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ARMAND Martine

INSERM Research Associate (CR1)
Languages: French (native), English (Professional working proficiency), Spanish
tel (crmbm) : +33 4 91 32 48 22
Key Words
- Lipids
- Phospholipids
- Cardiovascular diseases

Current Research Interest and projects

- Metabolism of lipids in cardiology (PUFA, DHA, Phospholipids, cardioprotection, metabolic programming)
- Nutritherapeutics
- Nutrients-Drugs co-therapy
- ‬Improve nutrition in different groups of population for preventing cardiovascular diseases.


- May 1992-September 1993: Post-Doctoral Fellow position in Clinical Nutrition at Georgetown University Medical Hospital, Department of Developmental Biology & Nutrition, Washington DC, USA.

- September 1988-April 1992: Ph.D. in Nutrition (Physico-chemical and enzymatic aspects of lipid digestion) at INSERM UMR 130 Human Nutrition & Lipids, Aix-Marseille Université (Université de la Méditerranée, ex-Aix-Marseille II), France.

- September 1985-June 1988: Master’s degree in Human Nutrition, Aix-Marseille Université (Université de St Jérôme, ex-Aix-Marseille III), France.

- September 1983-September 1985: Dietician-Nutritionist (BTS Diététique) at LET Marie Curie, Marseille, France.

- September 1980-June 1983: Bachelor’s degree (scientific field) at Lycée JH FABRE, Carpentras, France.

Research experiences

- Since January 2012: INSERM Research Scientist at CRMBM, CNRS (French National Centre for Scientific Research) UMR 7339, Team on Heart & Cardiovascular Diseases, Aix -Marseille Université (AMU).
  • Short description of the research projects: Metabolism of lipids in cardiology (PUFA, DHA, Phospholipids, cardioprotection, metabolic programming); Nutritherapeutics; Nutrients-Drugs co-therapy; ‬Improve nutrition in different groups of population for preventing diseases.

- 1996-2011: INSERM Research Scientist at French Institute of Health and Medical Research, UMR 476 Human Nutrition & Lipids, Aix -Marseille Université (AMU).

  • Short description of the research projects: Test of bioavailability of lipid nutrients; Physicochemical properties of lipids (boosters of digestive lipases); Recombinant lipase production; Elisa test; Clinical studies in nutrition, PUFA vector‬

- 1992-1993: Postdoctoral fellow at Georgetown University Medical Hospital Washington DC USA, Department of Developmental Biology and Nutrition, Pr Margit HAMOSH’s team.

  • Short description of the research projects: Clinical studies in Gastroenterology, in Neonatology, & at the Cystic Fibrosis Center (coll John’s Hopkins Hospital Baltimore); gastric lipase; Electron microscopy of milk fat globule (Coll NIH Bethesda)‬

Teaching experiences

- Since 2009: professional continuing education for Dieticians-Nutritionists organized by Journées Nationales de Diététique (Hôpital Ste Marguerite) under the responsibility of Pr Denis Raccah (Diabetology & Nutrition Department).
  • Short description of the lectures: different topics about Nutrition & Health (new topics each year); 15 lectures (2h each).

- Since 2004: Polytech AMU Marseille, School of Engineering, 5th year students in BIOTECHNOLOGY.

  • Short description of the lectures: Nutrition, Clinical Nutrition, Functional Foods, Nutrition & Genes (Epigenetics, nutrigenomics, nutrigenetics), Innovations in Nutrition & Industry (30 h).

- 1999-2014: L3 BIOLOGY UEBI615 in Nutrition, AMU Marseille.

  • Short description of the lectures: Dietetics and Nutrition, biochemistry, metabolism (6 credits, 75 hrs).

Awards and achievements

- September 2015: grant from Institut Danone-FRM for the research project on “Early PUFA status and cognitive/cardiovascular development in the french birth-cohort EDEN”.

- December 2011: prize from Baxter for the research project on “Consumption of different bioactive molecules from Human Milk & intestinal development in Very-Premature Newborns”.

- May 2005: award from Benjamin Delessert Institute for the work on “DHA in Human Milk “.

- September 1994: IFN (French Institute of Nutrition) Thesis prize.

- Janvier 1992: INSERM International Postdoctoral Fellowship.

- October 1991: Lavoisier prize for International Postdoctoral Fellowship.

Other websites

- LinkedIn
- Researchgate


- h-index: 28
- i10 index: 51
  • 56 original articles
  • 14 french revues
  • 8 Books/Chapters in Books
  • 31 abstracts in congress
  • 118 communications in congress (69 for international congress)
  • 28 invited communications/seminars.


Journal Article

  • Armand, M, Bernard, JY, Forhan, A, Heude, B, Charles, M-A & EDEN mother-child cohort study group, 2017, “Maternal nutritional determinants of colostrum fatty acids in the EDEN mother-child cohort”, Clinical Nutrition (Edinburgh, Scotland).
    Résumé : BACKGROUND & AIMS: Programming of infant development and later health may depend on early-milk polyunsaturated fatty acids (PUFA) contents, that are very variable between women for reasons not well elucidated. Indeed, a high n-6/n-3 PUFA in milk was associated with higher adiposity, arterial pressure and lower psychomotor scores in childhood. We aimed to explore the respective contribution of several maternal and perinatal factors to the variability of linoleic (LA), α-linolenic (ALA), arachidonic (AA), and docosahexaenoic (DHA) acid levels in early milk. METHODS: Fatty acids of 934 colostrum samples from the EDEN mother-child cohort were analyzed by gas chromatography. The dietary intakes during the last trimester of pregnancy were estimated using a quantitative food frequency questionnaire. Relationship between milk PUFA and dietary fatty acids, and other maternal or pregnancy variables were analyzed by multiple linear regression. RESULTS: The means (±SD) of colostrum LA, ALA, AA and DHA levels were, respectively, 9.85 ± 1.85, 0.65 ± 0.22, 0.86 ± 0.16, and 0.64 ± 0.19% of total fatty acids. Obese mothers colostrum contained the highest level of LA and AA and the lowest level of ALA and DHA. Colostrum LA, AA and DHA levels were higher in primiparous women. Mother's age was positively associated with colostrum AA and DHA. Dietary n-6 PUFA were associated with higher LA and lower DHA levels in colostrum, while dietary n-3 PUFA were related to higher LA and lower AA levels. Contrary to what was observed for DHA, AA level in colostrum was not related to its dietary intake. High dietary AA/DHA and total n-6/n-3 ratios were critical for the content of DHA in colostrum lipids. CONCLUSIONS: Our study brings new insights in the understanding of the main maternal factors involved in PUFA levels variability in early milk. These data are important to consider for dietary counseling for women prior to and during pregnancy.
    Mots-clés : BMI class, Cohort study, Colostrum PUFA, cvs, Maternal determinants, Pregnant women diet.


Journal Article

  • Bernard, JY, Armand, M, Forhan, A, De Agostini, M, Charles, M-A & Heude, B 2016, “Early life exposure to polyunsaturated fatty acids and psychomotor development in children from the EDEN mother-child cohort”, Ocl-Oilseeds and Fats Crops and Lipids, vol. 23, no. 1, p. D106.
    Résumé : Epidemiological studies have reported that breastfed children have improved psychomotor development compared to never breastfed children. Human studies suggest that polyunsaturated fatty acids (PUFA), especially long chain PUFA (LC-PUFA) which are highly contained in breast milk, could explain this link, since they are needed for pre-and postnatal brain development. Our aim was to study the relationships between several measures of pre-and postnatal exposures to PUFA and child's psychomotor development at 2 and 3 years in the EDEN cohort. We evaluated breastfeeding duration, colostrum PUFA levels and maternal dietary PUFA intake during pregnancy, that we related with three scores of psychomotor development, after taking into account potential confounders. Breastfeeding duration was positively associated with psychomotor development. No relationship was found with both pre-and postnatal exposure to LC-PUFA. However, the maternal dietary omega-6/omega-3 ratio was negatively associated with psychomotor development, mainly driven by intake in linoleic acid (LA). Among breastfed children, linoleic acid levels were negatively associated with psychomotor development. Furthermore, children exposed to the highest colostrum LA levels tended to score closer to never breastfed children than to children exposed to the lowest colostrums LA levels. Taken together, these results do not provide evidence in favour of a positive role of pre-and postnatal exposure to LC-PUFA on later psychomotor development, but highlight a potential negative role of being exposed in early life to high LA levels. From a public health perspective, this work reiterates the need to promote breastfeeding duration, and to monitor the balance of PUFA intake during pregnancy and lactation periods.
    Mots-clés : age, Brain, breast milk, breast-feeding duration, cognitive-development, Cohort Studies, cvs, docosahexaenoic acid, fish intake, iq, maternal nutrition, Milk, polyunsaturated fatty acids, Pregnancy, psychomotor development, requirements.

  • Bernard, M, Maixent, J-M, Gerbi, A, Lan, C, Cozzone, PJ, Pieroni, G, Armand, M & Coste, TC 2016, “Dietary docosahexaenoic acid-enriched glycerophospholipids exert cardioprotective effects in ouabain-treated rats via physiological and metabolic changes”, Food & Function, vol. 7, no. 2, p. 798-804.
    Résumé : Docosahexaenoic acid (DHA) might prevent heart failure or optimise drug treatments by improving cardiac contraction. We investigated whether DHA-enriched avian glycerophospholipids (GPL-DHA) exert cardioprotection in ouabain-treated rats after 4 weeks of dietary supplementation with 10, 35 or 60 mg DHA per kg body weight versus none (DHA10, DHA35, DHA60 and control groups, respectively). The contractile responsiveness to different doses of ouabain (10(-7) to 10(-4) M), ouabain intoxication (at 3 × 10(-4) M), and relative variations in cardiac energy metabolism were determined using (31)P NMR in isolated perfused rat hearts. The fatty acid composition of cardiac membranes was analysed by gas chromatography. DHA accretion in the heart was dose-dependent (+8%, +30% and +45% for DHA10, DHA35 and DHA60, respectively). The cardiac phosphocreatine content significantly increased at the baseline in DHA35 (+45%) and DHA60 groups (+85%), and at the different doses of ouabain in the DHA60 group (+73% to 98%). The maximum positive inotropy achieved at 10(-4) M ouabain was significantly increased in all DHA groups versus control (+150%, +122.5% and +135% for DHA10, DHA35 and DHA60, respectively), and ouabain intoxication was delayed. The increase in myocardial phosphocreatine content and the improved efficacy of ouabain on myocardial contraction without toxicity suggest the potential of GPL-DHA as a dietary supplement or ingredient for functional food, and possibly as a co-treatment with digitalis drugs in humans.
    Mots-clés : crmbm, snc.

  • Braud, L, Battault, S, Meyer, G, Nascimento, A, Gaillard, S, de Sousa, G, Rahmani, R, Riva, C, Armand, M, Maixent, J-M & Reboul, C 2016, “Antioxidant properties of tea blunt ROS-dependent lipogenesis: beneficial effect on hepatic steatosis in a high fat-high sucrose diet NAFLD obese rat model”, The Journal of Nutritional Biochemistry, vol. 40, p. 95-104.
    Résumé : Oxidative stress could trigger lipid accumulation in liver and thus hepatic steatosis. Tea is able to prevent liver disorders, but a direct link between antioxidant capacities and prevention of steatosis has not been reported yet. We aimed to investigate such relationship in a rat model of high fat-high sucrose diet (HFS)-induced obesity and to explore more deeply the mechanisms in isolated hepatocytes. Wistar rats were divided into a control group (standard diet), an HFS group (high fat-sucrose diet) and an HFS+tea group (HFS diet with ad-libitum access to tea drink). Body weight, fat mass, glycemic parameters in blood, lipid and oxidative stress parameters in blood and liver were measured in each group after 14 weeks. Isolated hepatocytes were treated with the reactive oxygen species (ROS) inducer t-BHP in the presence or not of antioxidants (tempol or tea), and superoxide anion production and lipid accumulation were measured using specific fluorescent probes. We reported that the HFS diet highly increased hepatic lipids content, while tea consumption attenuated steatosis and improved the oxidative status (decrease in hepatic oxidative stress, increase in plasma total antioxidant capacity). The role of antioxidant properties of tea in such phenomenon was confirmed in primary cultured rat hepatocytes. Indeed, the increase of mitochondrial ROS production with t-BHP resulted in lipid accumulation in hepatocytes (positive linear regression), and antioxidants (tempol or tea) normalized both. We reported that the antioxidant properties of tea protect rats from an obesogenic HFS diet-induced hepatic steatosis by counteracting the ROS-dependent lipogenesis.
    Mots-clés : Antilipogenesis, Antioxidant, Camellia sinensis, cvs, Mitochondrial ROS, NAFLD, Obesogenic diet.


Journal Article

  • Bernard, JY, Armand, M, Garcia, C, Forhan, A, De Agostini, M, Charles, M-A & Heude, B 2015, “The association between linoleic acid levels in colostrum and child cognition at 2 and 3 y in the EDEN cohort”, Pediatric Research, vol. 77, no. 6, p. 829-835.
    Résumé : BACKGROUND: Breastfeeding has been associated with improved cognitive development. This may be explained by polyunsaturated fatty acid (PUFA) content of breast milk, especially long-chain (LC) PUFA that are needed for postnatal brain growth. METHODS: Using data from the French EDEN cohort, we aimed to study whether the PUFA content of colostrum may explain observed associations between breastfeeding duration and cognitive scores at 2 and 3 y. A total of 709 breastfed children with available data on PUFA composition of milk were assessed using parent-reported questionnaires for motor and language at 2 y of age, or global cognition at 3 y. Multiple linear regressions were used to examine associations between PUFA levels and child cognitive scores, after controlling for many confounders. RESULTS: We found no association between LCPUFA levels in colostrum and child development. However, levels of linoleic acid (LA) were negatively associated with motor and cognitive scores, independently of breastfeeding duration. Children breastfed with the highest levels of LA tended to score closer to the never breastfed children than children breastfed with the lowest levels of LA. CONCLUSION: Our findings suggest that too high levels of LA in colostrum are associated with poorer child development at 2 and 3 y.
    Mots-clés : cvs.

  • Braud, L, Peyre, L, de Sousa, G, Armand, M, Rahmani, R & Maixent, J-M 2015, “Effect of Brewing Duration on the Antioxidant and Hepatoprotective Abilities of Tea Phenolic and Alkaloid Compounds in a t-BHP Oxidative Stress-Induced Rat Hepatocyte Model”, Molecules (Basel, Switzerland), vol. 20, no. 8, p. 14985-15002.
    Résumé : Tea is an interesting source of antioxidants capable of counteracting the oxidative stress implicated in liver diseases. We investigated the impact of antioxidant molecules provided by a mixture of teas' leaves (green, oolong, pu-erh) after different infusion durations in the prevention of oxidative stress in isolated rat hepatocytes, by comparison with pure epigallocatechin-3-gallate (EGCG), the main representative of tea catechins. Dried aqueous tea extracts (ATE) obtained after 5, 15 and 30 min infusion time were characterized for total polyphenols (gallic acid equivalent), catechins, gallic acid and caffeine (HPLC-DAD/ESI-MS) contents, and for scavenging ability against 2,2-diphenyl-1-picrylhydrazyl free radical. Hepatoprotection was evaluated through hepatocyte viability tests using tert-butyl hydroperoxide as a stress inducer, (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, neutral red uptake, real-time cellular impedance) and mitochondrial function tests. We showed that a 5-min incubation time is sufficient for an optimal bioaccessibility of tea compounds with the highest antioxidative ability, which decreases for longer durations. A 4-h pretreatment of cells with ATE significantly prevented cell death by regulating reactive oxygen species production and maintaining mitochondrial integrity. Pure EGCG, at doses similar in ATE (5-12 µM), was inefficient, suggesting a plausible synergy of several water-soluble tea compounds to explain the ATE beneficial effects.
    Mots-clés : cvs.


Journal Article
  • Armand, M & Flouris, AD 2013, “Effects of Milk Bioactive Compounds on Health”, Cellular and Molecular Biology, vol. 59, no. 1, p. 1-3.
  • Garcia, C, Duan, RD, Brévaut-Malaty, V, Gire, C, Millet, V, Simeoni, U, Bernard, M & Armand, M 2013, “Bioactive compounds in human milk and intestinal health and maturity in preterm newborn: an overview”, Cellular and Molecular Biology (Noisy-Le-Grand, France), vol. 59, no. 1, p. 108-131.
    Résumé : Premature births are increasing worldwide (about 15 millions per year) due to several reasons (an advanced maternal age, fertility treatments, stress, smoking, nutritional deficiencies) and lead to a high societal overall cost. Among neonatal care procedures, the clinical nutrition practices are essential to promote the development and to minimize the sequelae. Premature newborns are at major risk of death by infections due to the immaturity of their intestine. Human milk provides not only nutrients but also a plethora of biologically active components that are tailored to contribute to the development of the intestinal tract early in postnatal life. Among them, some bioactive molecules exhibit trophic effects (LC—PUFA, sphingomyelin, IGF—I and IGF—II, EGF, insulin, leptin, adiponectin, lactoferrin, lactadherin, probiotics, prebiotics, miRNA) or are part of the intestinal cell membranes (PUFA, LC—PUFA, phospholipids, sphingolipids, cholesterol), others educate the intestine for innate microbial recognition (sCD14, sTLR—2, miRNA), many of them display direct fighting against pathogens (some fatty acids and monoglycerides, some phospholipids and sphingolipids, BSSL, insulin, lactoferrin, sIgAs, MUC—1, lactadherin, probiotics, prebiotics), or contribute to establish the gut microbiota (LC—PUFA, lactoferrin, probiotics, prebiotics). A synergetic action exists between several bioactive molecules. All together these precious agents regulate the maturation of the intestinal mucosal barrier, and might program early in postnatal life the future adult intestinal health. This review lists the main bioactive compounds and addresses their plausible roles and mechanisms of action.
    Mots-clés : crmbm, Health, Humans, Infant, Newborn, Intestines, Macromolecular Substances, Milk, Human, Premature Birth.


Journal Article

  • Garcia, C, Lutz, NW, Confort-Gouny, S, Cozzone, PJ, Armand, M & Bernard, M 2012, “Phospholipid fingerprints of milk from different mammalians determined by 31P NMR: towards specific interest in human health”, Food Chemistry, vol. 135, no. 3, p. 1777-1783.
    Résumé : Our objective was to identify and quantify phospholipids in milk from different species (human HM, cow CoM, camel CaM, and mare MM) using an optimised (31)P NMR spectroscopy procedure. The phospholipid fingerprints were species-specific with a broader variety of classes found in HM and MM; HM and CaM were richer in sphingomyelin (78.3 and 117.5μg/ml) and plasmalogens (27.3 and 24μg/ml), possibly important for infant development. Total phospholipid content was higher in CaM (0.503mM) and lower in MM (0.101mM) compared to HM (0.324mM) or CoM (0.265mM). Our optimised method showed good sensitivity, high resolution, and easy sample preparation with minimal loss of target molecules. It is suitable for determining the accurate composition of a large number of bioactive phospholipids with putative health benefits, including plasmalogens, and should aid in selecting appropriate ingredient sources for infant milk substitutes or fortifiers, and for functional foods dedicated to adults.
    Mots-clés : Animals, Camels, crmbm, Humans, Magnetic Resonance Spectroscopy, Milk, Milk, Human, Phospholipids.


Journal Article

  • Garcia, C, Millet, V, Coste, TC, Mimoun, M, Ridet, A, Antona, C, Simeoni, U & Armand, M 2011, “French mothers' milk deficient in DHA contains phospholipid species of potential interest for infant development”, Journal of Pediatric Gastroenterology and Nutrition, vol. 53, no. 2, p. 206-212.
    Résumé : OBJECTIVES: An insufficient human milk docosahexaenoic acid (DHA) level was reported worldwide, which leads to the question of the sufficiency of the DHA supply for infant development in the French Mediterranean area. Also, among milk lipids, phospholipids may be of high potential interest for infant brain development, being a specific vector of DHA and providing plasmalogens. We aimed to estimate the consumption of such milk compounds by preterm and term infants. MATERIALS AND METHODS: Milk samples from 22 lactating French women living in a port city, Marseille, were collected in a neonatology department from a single full-breast expression using an electric pump. Amounts of triglycerides, total phospholipids and plasmalogens, and fatty acid profile were determined by gas chromatography, and cholesterol by enzymatic assay. RESULTS: Depending on the infant dietary guidelines we referred to, 46% or 82% of milk samples were below the recommended DHA level (0.4% or 0.7%), and a majority exhibited high linoleic acid/α-linolenic acid and n-6/n-3 ratios, probably resulting from high linoleic acid together with low fish and seafood products consumption. DHA carried by phospholipids in a majority of specimens met the requirements for brain development for term but not for premature infants. Milk plasmalogen levels ranged from 3.4 to 39.2  mg/L. CONCLUSIONS: Our results support the recommendation of DHA supplementation to French mothers living in a Mediterranean port city, and of decreased linoleic acid intake, to reach optimal milk composition for infant health. DHA-containing phospholipids including plasmalogen species may represent important bioactive human milk compounds.
    Mots-clés : Animals, Child Development, Colostrum, Dietary Fats, Docosahexaenoic Acids, Female, Fishes, France, Humans, Infant, Infant, Newborn, Infant, Premature, Male, Maternal Nutritional Physiological Phenomena, Milk, Human, Nutritional Requirements, Nutritive Value, Phospholipids, Plasmalogens, Premature Birth, Reproducibility of Results, Seafood, Triglycerides.


Journal Article

  • Mimoun, M, Coste, TC, Lebacq, J, Lebecque, P, Wallemacq, P, Leal, T & Armand, M 2009, “Increased tissue arachidonic acid and reduced linoleic acid in a mouse model of cystic fibrosis are reversed by supplemental glycerophospholipids enriched in docosahexaenoic acid”, The Journal of Nutrition, vol. 139, no. 12, p. 2358-2364.
    Résumé : An imbalance in (n-6)/(n-3) PUFA has been reported in cystic fibrosis (CF) patients. Glycerophospholipids enriched in docosahexaenoic acid (GPL-DHA) have been shown to regulate the (n-6)/(n-3) fatty acid ratio in the elderly. Here, we tested the effect of GPL-DHA supplementation on PUFA status in F508del homozygous CF mice. GPL-DHA liposomes were administrated by gavage (60 mg DHA/kg daily, i.e. at maximum 1.4 mg DHA/d) to 1.5-mo-old CF mice (CF+DHA) and their corresponding wild-type (WT) homozygous littermates (WT+DHA) for 6 wk. The PUFA status of different tissues was determined by GC and compared with control groups (CF and WT). There was an alteration in the (n-6) PUFA pathway in several CF-target organs in CF compared with WT mice, as evidenced by a higher level of arachidonic acid (AA) in membrane phospholipids or whole tissue (21 and 39% in duodenum-jejunum, 32 and 38% in ileum, and 19 and 43% in pancreas). Elevated AA levels were associated with lower linoleic acid (LA) and higher dihomo-gamma-linolenic acid levels. No DHA deficiency was observed. GPL-DHA treatment resulted in different PUFA composition changes depending on the tissue (increase in LA, decrease in elevated AA, DHA increase, increase in (n-6)/(n-3) fatty acid ratio). However, the DHA/AA ratio consistently increased in all tissues in CF+DHA and WT+DHA mice. Our study demonstrates the effectiveness of an original oral DHA formulation in counter-balancing the abnormal (n-6) fatty acid metabolism in organs of CF mice when administrated at a low dose and highlights the potential of the use of GPL-DHA as nutritherapy for CF patients.
    Mots-clés : Animals, Arachidonic Acid, Cell Membrane, Cystic Fibrosis, Dietary Supplements, Disease Models, Animal, Docosahexaenoic Acids, Fatty Acids, Fatty Acids, Omega-3, Fatty Acids, Omega-6, Glycerophospholipids, Humans, Intestines, Linoleic Acid, Lipids, Lung, Mice, Mice, Inbred Strains, Pancreas, Phospholipids, Sequence Deletion.


Journal Article

  • Coste, TC, Armand, M, Lebacq, J, Lebecque, P, Wallemacq, P & Leal, T 2007, “An overview of monitoring and supplementation of omega 3 fatty acids in cystic fibrosis”, Clinical Biochemistry, vol. 40, no. 8, p. 511-520.
    Résumé : Essential fatty acid deficiency has been increasingly reported in patients with cystic fibrosis. The purpose of this work is to critically summarize previous data on fatty acid status and omega3 supplementation in cystic fibrosis. Although the reported abnormalities differ from study to study, the two most consistent features appeared to be reduced circulating levels of linoleic acid and docosahexaenoic acid (DHA). On the assumption that the fatty acid composition of erythrocyte cell membranes may be similar to that of other organs, it seems appropriate to monitor the phospholipid profile from erythrocyte membranes together with circulating blood levels. Formulations containing widely variable DHA doses, ranging from 300 mg to 5 g per day, have been administered to patients with cystic fibrosis with discrepant outcomes. Randomized controlled trials are needed in order to draw firm conclusions on the therapeutic effect of omega3 fatty acid supplementation in cystic fibrosis.
    Mots-clés : Cystic Fibrosis, Dietary Supplements, Docosahexaenoic Acids, Drug Monitoring, Fatty Acids, Omega-3, Fatty Acids, Unsaturated, Humans, Models, Biological.

  • Favé, G, Oliver, P, Mimoun, M, Millet, V, Miralles, O, Ridet, A, Gleize, B, Pico, C, Palou, A, Coste, TC & Armand, M 2007, “Nutritional quality of human milk from Mediterranean lactating women: a preliminary approach towards personalised nutrition”, Genes & Nutrition, vol. 2, no. 1, p. 95-98.


Journal Article

  • Armand, M, Hamosh, M, Philpott, JR, Resnik, AK, Rosenstein, BJ, Hamosh, A, Perman, JA & Hamosh, P 2004, “Gastric function in children with cystic fibrosis: effect of diet on gastric lipase levels and fat digestion”, Pediatric Research, vol. 55, no. 3, p. 457-465.
    Résumé : The effect of diet, usual (44 +/- 4% energy as fat), high-fat (49 +/- 4% energy as fat), and moderate-fat (33 +/- 2% energy as fat), on gastric function (lipase and pepsin activities, pH, emptying rate) and intragastric digestion of fat were assessed in six children with cystic fibrosis. Fasting and postprandial activity of digestive enzymes, gastric pH, and gastric volume measured before, during, and after 120 min of feeding did not differ significantly as a function of fat intake. Postprandial gastric lipase output (units per kilogram of body weight) during usual, moderate-fat, and high-fat diets was close to or higher than (38.8 +/- 7.2, 44.9 +/- 8.6, and 54.8 +/- 5.5 U/kg per 20 min) gastric lipase output of premature infants (22.5 +/- 6.4 to 28.3 +/- 6.6 U/kg per 20 min) or of healthy adults (5.4 +/- 0.4 U/kg per 15 min) fed a high-fat diet. Postprandial pepsin output was higher (4749 +/- 797, 6117 +/- 925, and 5444 +/- 819 U/kg per 20 min) than in premature infants (597 +/- 77 to 743 +/- 97 U/kg per 20 min) or healthy adults (781 +/- 56 U/kg per 15 min). Eighty minutes after feeding gastric lipolysis reached 20 to 36%. This study shows that gastric lipase activity is high in cystic fibrosis patients maintained on diets providing 32% to 49% energy as fat, and that gastric lipase level did not increase over the ranges of dietary fat intake tested.
    Mots-clés : Adolescent, Child, Child, Preschool, Cystic Fibrosis, Diet, Fats, Female, Gastric Emptying, Humans, Hydrogen-Ion Concentration, Lipase, Male, Pepsin A, Postprandial Period, Stomach.
  • Favé, G, Coste, TC & Armand, M 2004, “Physicochemical properties of lipids: new strategies to manage fatty acid bioavailability”, Cellular and Molecular Biology (Noisy-Le-Grand, France), vol. 50, no. 7, p. 815-831.
    Résumé : Fatty acid bioavailability can be managed through the physicochemical properties of lipid such as lipid-droplet size, lipid-droplet ultrastructure (lipids organization between core and surface), structure of triglycerides and of phospholipids. The lipid-droplet size exhibits a major effect on lipase activity during lipid digestion. The lipid-droplet ultrastructure is a dynamic factor controling lipase interaction at the lipid interface via the surface phospholipid layer, and also lipase activity via the proportion of triglyceride molecules able to locate at the surface. Triglyceride structure affects in a strong manner digestion, absorption and fatty acid metabolism. Finally, optimal fatty acid transport to specific tissues is dependent on the vehicle molecule (triglyceride or ethyl ester or phospholipid). All these aspects provide convincing support for the possibility of using biotechnologically remodeled lipids with specific physicochemical properties for health benefits.
    Mots-clés : Animals, Biological Availability, Chemistry, Physical, Emulsions, Fatty Acids, Humans, Lipase, Lipids, Microscopy, Electron, Milk, Models, Chemical, Phospholipids, Physicochemical Phenomena, Triglycerides.


Journal Article

  • Pafumi, Y, Lairon, D, de la Porte, PL, Juhel, C, Storch, J, Hamosh, M & Armand, M 2002, “Mechanisms of inhibition of triacylglycerol hydrolysis by human gastric lipase”, The Journal of Biological Chemistry, vol. 277, no. 31, p. 28070-28079.
    Résumé : In the human stomach, gastric lipase hydrolyzes only 10 to 30% of ingested triacylglycerols because of an inhibition process induced by the long chain free fatty acids generated, which are mostly protonated at gastric pH. The aim of this work was to elucidate the mechanisms by which free fatty acids inhibit further hydrolysis. In vitro experiments examined gastric lipolysis of differently sized phospholipid-triolein emulsions by human gastric juice or purified human gastric lipase, under close to physiological conditions. The lipolysis process was further investigated by scanning electron microscopy, and gastric lipase and free fatty acid movement during lipolysis were followed by fluorescence microscopy. The results demonstrate that: 1) free fatty acids generated during lipolysis partition between the surface and core of lipid droplets with a molar phase distribution coefficient of 7.4 at pH 5.40; 2) the long chain free fatty acids have an inhibitory effect only when generated during lipolysis; 3) inhibition of gastric lipolysis can be delayed by the use of lipid emulsions composed of small-size lipid droplets; 4) the release of free fatty acids during lipolysis induces a marked increase in droplet surface area, leading to the formation of novel particles at the lipid droplet surface; and 5) the gastric lipase is trapped in these free fatty acid-rich particles during their formation. In conclusion, we propose a model in which the sequential physicochemical events occurring during gastric lipolysis lead to the inhibition of further triacylglycerol lipolysis.
    Mots-clés : Adult, Emulsions, Gastric Juice, Homeostasis, Humans, Hydrolysis, Kinetics, Lipase, Lipolysis, Triglycerides.


Journal Article
  • Borel, P, Pasquier, B, Armand, M, Tyssandier, V, Grolier, P, Alexandre-Gouabau, MC, Andre, M, Senft, M, Peyrot, J, Jaussan, V, Lairon, D & Azais-Braesco, V 2001, “Processing of vitamin A and E in the human gastrointestinal tract”, American Journal of Physiology. Gastrointestinal and Liver Physiology, vol. 280, no. 1, p. G95-G103.
    Résumé : We aimed to provide basic data on the processing of vitamin A and E in the human gastrointestinal tract and to assess whether the size of emulsion fat globules affects the bioavailability of these vitamins. Eight healthy men received intragastrically two lipid formulas differing in their fat-globule median diameter (0.7 vs. 10. 1 microm. Formulas provided 28 mg vitamin A as retinyl palmitate and 440 mg vitamin E as all-rac alpha-tocopherol. Vitamins were measured in gastric and duodenal aspirates, as well as in chylomicrons, during the postprandial period. The gastric emptying rate of lipids and vitamin A and E was similar. The free retinol/total vitamin A ratio was not significantly modified in the stomach, whereas it was dramatically increased in the duodenum. The proportion of ingested lipid and vitamins was very similar in the duodenal content. The chylomicron response of lipids and vitamins was not significantly different between the two emulsions. Our main conclusions are as follows: 1) there is no significant metabolism of vitamin A and E in the human stomach, 2) the enzyme(s) present in the duodenal lumen is significantly involved in the hydrolysis of retinyl esters, and 3) the size of emulsion fat globules has no major effect on the overall absorption of vitamin A and E.
    Mots-clés : Adult, Chylomicrons, Digestion, Duodenum, Emulsions, Fatty Acids, Gastric Emptying, Humans, Hydrogen-Ion Concentration, Hydrolysis, Intestinal Absorption, Lipase, Male, Micelles, Pancreas, Particle Size, Triglycerides, Vitamin A, Vitamin E.


Journal Article
  • Juhel, C, Armand, M, Pafumi, Y, Rosier, C, Vandermander, J & Lairon, D 2000, “Green tea extract (AR25) inhibits lipolysis of triglycerides in gastric and duodenal medium in vitro”, The Journal of Nutritional Biochemistry, vol. 11, no. 1, p. 45-51.
    Résumé : In this study, we aimed to evaluate in vitro the inhibitory activity of a green tea extract (AR25 standardized at 25% catechins) on gastric and pancreatic lipase activities. We first used tributyrin as a substrate to evaluate the capability of AR25 to induce digestive lipase inhibition. Gastric lipase was totally inhibited by 40 mg AR25/g tributyrin whereas pancreatic lipase inhibition was maximum (78.8 +/- 0.7%) with 80 mg AR25/g tributyrin. We then used triolein, a long-chain triglyceride, to check whether AR25 could alter lipase activities on a physiologic substrate. AR25 60 mg/g triolein induced a dramatic inhibition of gastric lipase (96.8 +/- 0.4%) whereas pancreatic lipase activity was partially reduced (66.50 +/- 0.92%). Finally, the concerted action of gastric and pancreatic lipases was studied with an excess of enzymes to mimic the physiologic conditions observed in vivo. Incubation of AR25 with an excess of digestive lipases resulted in a drastic decrease in gastric lipolysis but the inhibitory effect on pancreatic lipase was less marked. On the whole, as compared to the control, lipolysis of triolein under the successive action of the two digestive lipases was reduced by 37 +/- 0.6% in the presence of AR25. Because a lipid/water interface is necessary for lipolysis to occur, lipid emulsification and emulsion droplet size were measured in gastric and duodenal media in the presence of AR25. In gastric and duodenal conditions, AR25 inhibited the lipid emulsification process. From these data we conclude that (1) in vitro, fat digestion is significantly inhibited by 60 mg AR25/g triolein, and (2) gastric as well as pancreatic lipase inhibition could be related to altered lipid emulsification in gastric or duodenal media. The green tea extract AR25 exhibiting marked inhibition of digestive lipases in vitro is likely to reduce fat digestion in humans.


Journal Article
  • Armand, M, Pasquier, B, André, M, Borel, P, Senft, M, Peyrot, J, Salducci, J, Portugal, H, Jaussan, V & Lairon, D 1999, “Digestion and absorption of 2 fat emulsions with different droplet sizes in the human digestive tract”, The American Journal of Clinical Nutrition, vol. 70, no. 6, p. 1096-1106.
    Résumé : BACKGROUND: The extent of fat emulsification affects the activity of digestive lipases in vitro and may govern digestion and absorption of dietary fat. OBJECTIVE: We investigated the effect of the fat globule size of 2 enteral emulsions on fat digestion and assimilation in humans. DESIGN: Healthy subjects received intragastrically a coarse (10 microm) and a fine (0.7 microm) lipid emulsion of identical composition in random order. Gastric and duodenal aspirates were collected throughout digestion to measure changes in fat droplet size, gastric and pancreatic lipase activities, and fat digestion. Blood lipids were measured postprandially for fat assimilation. RESULTS: Despite an increase in droplet size in the stomach (2.75-6.20 microm), the fine emulsion retained droplets of smaller size and its lipolysis was greater than that of the coarse emulsion (36.5% compared with 15.8%; P < 0.05). In the duodenum, lipolysis of the fine emulsion was on the whole higher (73.3% compared with 46.3%). The overall 0-7-h plasma and chylomicron responses given by the areas under the curve were not significantly different between the emulsions, but the triacylglycerol peak was delayed with the fine emulsion (3 h 56 min compared with 2 h 50 min). CONCLUSIONS: Fat emulsions behave differently in the digestive tract depending on their initial physicochemical properties. A lower initial fat droplet size facilitates fat digestion by gastric lipase in the stomach and duodenal lipolysis. Overall fat assimilation in healthy subjects is not affected by differences in initial droplet size because of efficient fat digestion by pancreatic lipase in the small intestine. Nevertheless, these new observations could be of interest in the enteral nutrition of subjects suffering from pancreatic insufficiency.
    Mots-clés : Absorption, Adult, Chylomicrons, Dietary Fats, Digestion, Duodenum, Emulsions, Gastrointestinal Contents, Humans, Intubation, Gastrointestinal, Lipids, Lipolysis, Male, Micelles, Particle Size, Postprandial Period, Stomach, Time Factors, Triglycerides.


Journal Article
  • Dubois, C, Beaumier, G, Juhel, C, Armand, M, Portugal, H, Pauli, AM, Borel, P, Latgé, C & Lairon, D 1998, “Effects of graded amounts (0-50 g) of dietary fat on postprandial lipemia and lipoproteins in normolipidemic adults”, The American Journal of Clinical Nutrition, vol. 67, no. 1, p. 31-38.
    Résumé : Eight normolipidemic males ingested on separate days and in a random order five mixed meals containing 0, 15, 30, 40, or 50 g fat. Fasting and postprandial blood samples were obtained for 7 h and chylomicrons and lipoproteins were isolated. The nonfat and 15-g fat meals did not generate noticeable postprandial variations except for HDL phospholipids (P < 0.05). The serum and chylomicron triacylglycerol responses obtained after the meals correlated positively with the amount of fat ingested and peaked after 2-3 h. Serum free cholesterol and phospholipids increased and esterified cholesterol decreased postprandially in a dose-response manner. At the same time, triacylglycerol-rich-lipoprotein triacylglycerols, esterified cholesterol, LDL free cholesterol, HDL triacylglycerols, phospholipids, and free cholesterol increased whereas LDL and HDL esterified cholesterol decreased when the amount of ingested fat increased. The data showed that increasing the amount of fat in the usual range of ingestion (0-50 g) led to stepwise increases in the postprandial rise of chylomicron and serum triacylglycerols and induced marked changes in serum lipoproteins postprandially. The existence of a no-effect level of dietary fat (15 g) on postprandial lipemia and lipoproteins in healthy adults was shown.
    Mots-clés : Adult, Cholesterol, Chylomicrons, Dietary Fats, Humans, Insulin, Linear Models, Lipid Metabolism, Lipids, Lipoproteins, Male, Phospholipids, Postprandial Period, Time Factors, Triglycerides.


Journal Article
  • Borel, P, Mekki, N, Boirie, Y, Partier, A, Grolier, P, Alexandre-Gouabau, MC, Beaufrere, B, Armand, M, Lairon, D & Azais-Braesco, V 1997, “Postprandial chylomicron and plasma vitamin E responses in healthy older subjects compared with younger ones”, European Journal of Clinical Investigation, vol. 27, no. 10, p. 812-821.
    Résumé : The effect of ageing on vitamin E bioavailability in humans was assessed by comparing chylomicron and plasma alpha-tocopherol postprandial concentrations after a dose of vitamin E (432 or 937 IU as d1-alpha-tocopherol acetate), in eight young (20-30 years old) and eight healthy elderly men (64-72 years old). The fasting plasma alpha-tocopherol concentration was significantly higher in the elderly (33 +/- 2 mumol L-1) than in the young (22 +/- 2 mumol L-1). In both groups, the plasma and chylomicron alpha-tocopherol postprandial concentrations were significantly, approximately twofold, higher after the 937-IU meal than after the 432-IU meal. For both test meals, the chylomicron alpha-tocopherol areas under the curve were significantly lower in the elderly than in the young subjects: 98.9 +/- 16.5 (young group) vs. 55.3 +/- 7.8 (elderly group) mumol L-1 h for the 937-IU test meal and 60.4 +/- 14.1 (young group) vs. 26.0 +/- 7.6 (elderly group) mumol L-1 h for the 432-IU test meal, whereas the plasma alpha-tocopherol area under the curve was significantly higher in elderly than in young subjects: 337.56 +/- 16.11 (937-IU test meal) vs. 159.81 +/- 35.55 (432-IU test meal) mumol L-1 h in the young group and 709.55 +/- 69.33 (937-IU test meal) vs. 436.39 +/- 41.08 (432-IU test meal) mumol L-1 h in the elderly group. We concluded that (a) the amount of vitamin E appearing in plasma is proportional to the dose ingested (up to 937 IU); (b) the intestinal absorption of vitamin E is not increased, even possibly decreased, in the elderly; and (c) the amount of vitamin E transported by non-chylomicron lipoproteins is apparently higher in the elderly. This suggests that vitamin E postprandial transport is affected by ageing, mainly as the consequence of age-related modifications of lipoprotein metabolism.
    Mots-clés : Adult, Age Factors, Aged, Biological Availability, Chylomicrons, Humans, Lipids, Male, Middle Aged, Postprandial Period, Vitamin A, Vitamin E.


Journal Article
  • Armand, M, Borel, P, Pasquier, B, Dubois, C, Senft, M, Andre, M, Peyrot, J, Salducci, J & Lairon, D 1996, “Physicochemical characteristics of emulsions during fat digestion in human stomach and duodenum”, The American Journal of Physiology, vol. 271, no. 1 Pt 1, p. G172-183.
    Résumé : Seven fasting subjects were fitted with nasogastric and nasoduodenal tubes and received intragastrically a coarsely emulsified test meal. Gastric and duodenal aspirates were collected after 1, 2, 3, and 4 h. In the duodenum, most lipids (> 90%) were present as emulsified droplets 1-100 microns in size. Large droplets and unemulsified material present in the test meal (> 100 micron) disappeared, whereas smaller droplets (1-50 microns) were generated after 1 h of digestion. Thus the median lipid droplet diameter significantly decreased (19.6 vs. 56.5 microns in the test meal) and the droplet surface area significantly increased (1.58 vs. 0.70 micron2/g fat). Intermediate droplet diameters were 34.3, 46.3, and 27.6 microns after 2, 3, and 4 h, respectively. In the stomach, a comparable emulsion particle size pattern was observed, with median droplet diameters of 17.2, 37.9, 52.4, and 41.6 microns after 1, 2, 3, and 4 h, respectively. However, the extent of triglyceride hydrolysis was much lower in the stomach (6-16%) than in the duodenum (42-45%), where small droplets were enriched in lipolytic products, cholesterol, and phospholipids. The present findings show for the first time that most dietary lipids are present in the human duodenum as emulsified droplets 1-50 microns in size and that no further marked emulsification of dietary fat occurs in the duodenum compared with the stomach.
    Mots-clés : Adult, Bile, Chemistry, Physical, Colipases, Dietary Fats, Digestion, Duodenum, Emulsions, Fats, Gastrointestinal Contents, Humans, Hydrogen-Ion Concentration, Lipase, Lipolysis, Male, Osmolar Concentration, Particle Size, Physicochemical Phenomena, Stomach, Tissue Distribution, Triglycerides.

  • Armand, M, Hamosh, M, Mehta, NR, Angelus, PA, Philpott, JR, Henderson, TR, Dwyer, NK, Lairon, D & Hamosh, P 1996, “Effect of human milk or formula on gastric function and fat digestion in the premature infant”, Pediatric Research, vol. 40, no. 3, p. 429-437.
    Résumé : The effect of diet, human milk or formula, on gastric function (lipase and pepsin activity, pH, and volume) and intragastric digestion of fat was assessed in 28 appropriate for gestational age preterm infants (gestational age, 28.9 +/- 1.4, 29.1 +/- 0.9, 29.5 +/- 0.6 wk; birth weight, 1.00 +/- 0.14 to 1.18 +/- 0.07 kg). The infants were fed either human milk (n = 11), SMA Super Preemie formula (n = 9), or Similac, Special Care formula (n = 8). Fasting and postprandial activity of digestive enzymes, pH, and gastric volume (measured before or during 50 min after gavage feeding) did not differ as a function of diet among the three groups of infants. Gastric lipase output, 23.1 +/- 5.1, 28.3 +/- 6.6, and 22.5 +/- 6.4 (U/kg of body weight) in human milk-, SMA SP-, or Similac SC-fed infants was comparable to the gastric lipase output of healthy adults fed a high fat diet (22.6 +/- 3.0). Pepsin output was, however, significantly lower (597 +/- 77, 743 +/- 97, and 639 +/- 142 U/kg of body weight) in human milk-, SMA SP-, and Similac SC-fed infants) than in healthy adults (3352 +/- 753 U/kg). The hydrolysis of dietary fat was 1.7-2.5-fold higher (p < 0.01) in human milk-fed infants than in infants fed either formula. We conclude that differences in type of feeding, i.e. different fatty acid profiles (long chain or medium chain triglycerides), different emulsions (natural or artificial), and different fat particle sizes do not affect the level of activity of gastric enzymes. However, the triglyceride within milk fat globules appears to be more accessible to gastric lipase than that within formula fat particles. We suggest that the contribution of gastric lipase to overall fat digestion might be greater in the newborn (a period of pancreatic insufficiency) than in the adult.
    Mots-clés : Dietary Fats, Digestion, Evaluation Studies as Topic, Female, Humans, Hydrogen-Ion Concentration, Infant Food, Infant, Newborn, Infant, Premature, Intestinal Absorption, Lipase, Lipolysis, Male, Milk, Human, Pepsin A, Stomach.
  • Borel, P, Grolier, P, Armand, M, Partier, A, Lafont, H, Lairon, D & Azais-Braesco, V 1996, “Carotenoids in biological emulsions: solubility, surface-to-core distribution, and release from lipid droplets”, Journal of Lipid Research, vol. 37, no. 2, p. 250-261.
    Résumé : Data on the physico-chemical properties of carotenoids in biological emulsions are essential to our knowledge of carotenoid metabolism. Therefore, we determined the behavior of carotenoids in phospholipid-stabilized triglyceride emulsions, a model for biological emulsions such as dietary emulsions, triglyceride-rich lipoproteins, and intracellular storage droplets. The solubility of beta-carotene (a model for apolar carotenoids, carotenes) in pure bulk triglycerides (0.112 to 0.141 wt % according to triglycerides) was significantly higher than zeaxanthin (a model for polar carotenoids, xanthophylls) (0.022 to 0.088 wt %). The solubility of both carotenoids increased when the chain-length of the triglycerides' fatty acids decreased. The amount of zeaxanthin associated with lipid droplet dramatically increased in phospholipid-triglyceride droplets as compared to the pure corresponding triglyceride droplets, whereas the amount of beta-carotene associated with lipid droplets increased only slightly beta-Carotene distributed almost exclusively in the core of triolein-lecithin-carotenoid droplets, while zeaxanthin distributed preferentially at the droplet's surface. A significant percentage (8.3%) of zeaxanthin was spontaneously transferred from lipid droplets to aqueous phase and the remaining part was transferred during triglyceride hydrolysis catalysed by pancreatic lipase, while beta-carotene absolutely required triglyceride lipolysis to be transferred to the aqueous phase. Our results show that polar and apolar carotenoids behave differently in biological emulsions. They further our understanding of the bioavailability of polar and apolar carotenoids and of their distribution between lipoprotein particles.
    Mots-clés : Animals, beta Carotene, Carotenoids, Chemistry, Physical, Emulsions, Lipase, Lipids, Lipolysis, Pancreas, Phospholipids, Physicochemical Phenomena, Solubility, Swine, Temperature, Triglycerides, Triolein, Xanthophylls, Zeaxanthins.
  • Dubois, C, Armand, M, Ferezou, J, Beaumier, G, Portugal, H, Pauli, AM, Bernard, PM, Becue, T, Lafont, H & Lairon, D 1996, “Postprandial appearance of dietary deuterated cholesterol in the chylomicron fraction and whole plasma in healthy subjects”, The American Journal of Clinical Nutrition, vol. 64, no. 1, p. 47-52.
    Résumé : This study examined the appearance of dietary cholesterol in the chylomicron fraction (chylomicrons plus chylomicron remnants) and whole plasma in healthy normolipidemic subjects during a 0-7-h postprandial period. Six adult males were given two diet sequences in random order: a low-fiber diet (standard Western diet for 14 d) followed by a labeled low-fiber test meal or a fiber-supplemented diet (40 g oat bran/d for 14 d) followed by a labeled oat bran (40 g) test meal. The test meals provided 192.5 mg cholesterol, including 80.1 mg octadeuterated cholesterol. Fasting and hourly postmeal blood samples were obtained for 7 h. Isotopic cholesterol ratios [tracer:(tracer+native cholesterol)] were determined by gas chromatography-mass spectrometry. Chylomicron triacylglycerol and cholesterol concentrations peaked after 2-3 h and returned to baseline after 7 h. After the low-fiber test meal, the isotopic cholesterol ratio continuously increased until 7 h in the chylomicron fraction (4.2 +/- 1.2 x 10(-3)) and whole plasma (1.04 +/- 0.39 x 10(-3)). At 7 h postprandial, the maximum dietary cholesterol concentration in the chylomicron fraction and plasma cholesterol was 1 in 99 and 1 in 397 cholesterol molecules, respectively. No marked differences were obtained after the high-fiber sequence compared with the low-fiber one; there was a comparable isotopic cholesterol ratio and concentration in the chylomicron fraction and a slightly lower (-44%, P < 0.10) 0-7 h area under the curve whole-plasma deuterated cholesterol concentration. Thus, dietary cholesterol supplied as a single meal does not simultaneously appear in the chylomicron fraction postprandially with endogenous cholesterol and triacylglycerols and fiber feeding does not markedly alter this process in healthy normolipidemic humans.
    Mots-clés : Adult, Cholesterol, Dietary, Chylomicrons, Deuterium, Food, Humans, Kinetics, Male, Triglycerides.
  • Pasquier, B, Armand, M, Castelain, C, Guillon, F, Borel, P, Lafont, H & Lairon, D 1996, “Emulsification and lipolysis of triacylglycerols are altered by viscous soluble dietary fibres in acidic gastric medium in vitro”, The Biochemical Journal, vol. 314 ( Pt 1), p. 269-275.
    Résumé : This in vitro study was designed to test the hypothesis that soluble dietary fibres can alter the process of intragastric lipid emulsification and possibly subsequent triacylglycerol lipolysis. Three guar gums, two pectins and gum arabic were dissolved in acidic gastric medium in the concentration range 0.3-2.0% (w/v). Viscosities of fibre solutions were measured and apparent viscosities varied over a wide range (0.7-77 mPa/s). Emulsification of a lipid mixture (triolein/phosphatidylcholine/cholesterol) was performed under mild conditions in the presence of increasing concentrations of soluble fibres. The amount of emulsified lipid was not affected whereas the size of the emulsified droplets was increased by raising the concentration of viscous fibres only. The droplet size (r=0.75, P=0.006) and overall droplet surface area (r=-0.69, P=0.009) were strongly correlated with the medium viscosity in the range 0-20 mPa/s. The addition of solutions of viscous fibres to a preformed standard emulsion did not change the initial velocity of human gastric lipase reaction. Conversely, when emulsions prepared in the presence of fibres (i.e. with different droplet sizes) were incubated with excess gastric enzyme for 2 h, the high-viscosity guar gum significantly reduced the extent of triacylglycerol lipolysis, as compared with control and low- or medium-viscosity fibres. In conclusion, the data obtained show that reducing emulsification of dietary lipids in the mildly acid medium found in the stomach is a mechanism by which soluble viscous fibres can alter lipid assimilation.
    Mots-clés : Dietary Fiber, Emulsions, Galactans, Gastric Acid, Gastric Juice, Humans, Hydrogen-Ion Concentration, Lipase, Lipid Metabolism, Lipolysis, Mannans, Particle Size, Pectins, Plant Gums, Solubility, Viscosity.


Journal Article
  • Armand, M, Hamosh, M, DiPalma, JS, Gallagher, J, Benjamin, SB, Philpott, JR, Lairon, D & Hamosh, P 1995, “Dietary fat modulates gastric lipase activity in healthy humans”, The American Journal of Clinical Nutrition, vol. 62, no. 1, p. 74-80.
    Résumé : The aim of this study was to determine whether the amount of dietary fat modulates the activity of gastric lipase in humans. Gastric juice was collected from six healthy subjects after 2-wk periods of either a high-fat (50% of energy as fat) or low-fat (25% of energy as fat) diet. The collection period lasted 2 h, the first hour under baseline conditions and the second hour after pentagastrin stimulation (6 micrograms/kg body wt). Gastric lipase and pepsin activities were quantitated at 15-min intervals and total enzyme outputs were calculated. Under baseline conditions there was a tendency for higher output of gastric lipase and pepsin after the high-fat diet than after the low-fat diet (gastric lipase: 745 compared with 446 U/h, pepsin: 107,677 compared with 78,505 U/h). The difference in output between diet groups was significant after pentagastrin stimulation (gastric lipase: 1323 compared with 875 U/h, pepsin: 191,751 compared with 128,961 U/h, for high-fat compared with low-fat diet, respectively, P < 0.05). This study is the first to report that a high-fat diet leads to an increase in the activity of gastric enzymes in humans.
    Mots-clés : Adaptation, Physiological, Adult, Diet, Fat-Restricted, Dietary Fats, Female, Gastric Acidity Determination, Gastric Juice, Humans, Linear Models, Lipase, Male, Pentagastrin, Pepsin A.
  • Dubois, C, Armand, M, Senft, M, Portugal, H, Pauli, AM, Bernard, PM, Lafont, H & Lairon, D 1995, “Chronic oat bran intake alters postprandial lipemia and lipoproteins in healthy adults”, The American Journal of Clinical Nutrition, vol. 61, no. 2, p. 325-333.
    Résumé : This study evaluates the possible interaction between chronic oat bran intake and the postmeal metabolic response. Six normolipidemic men consumed three different diets for 14 d, at the end of which they consumed a test meal. The diets were C (control), basal low-fiber diet (15.6 g fiber/d) and a low-fiber (2.8 g fiber) test meal; OB (oat bran), basal low-fiber diet and a 40-g oat bran-enriched test meal (12.8 g fiber); and OB-A (oat bran-adaptation), 14-d oat bran (40 g/d) supplemented diet (23.8 g fiber/d) and an oat bran test meal (12.8 g fiber). The diets were fed in a random order. Fasting and postmeal blood samples were obtained for 7 h and lipoproteins were isolated. Adding oat bran to the test meals markedly reduced the postmeal insulin rise (P < 0.05). Compared with the low-fiber control diet, the effects elicited postprandially by adding oat bran to a single meal were enhanced after 14 d of oat bran feeding, ie, increased plasma triglycerides, phospholipids, and free cholesterol; decreased plasma esterified cholesterol; increased chylomicron and small-sized triglyceride-rich lipoprotein triglycerides; increased LDL and HDL free cholesterol; and decreased HDL esterified cholesterol. Thus, chronic oat bran feeding alters the postmeal response in human subjects.
    Mots-clés : Adult, Avena sativa, Cholesterol, Dietary Fiber, Eating, Humans, Insulin, Lipoproteins, Male, Triglycerides.


Journal Article
  • Armand, M, Borel, P, Dubois, C, Senft, M, Peyrot, J, Salducci, J, Lafont, H & Lairon, D 1994, “Characterization of emulsions and lipolysis of dietary lipids in the human stomach”, The American Journal of Physiology, vol. 266, no. 3 Pt 1, p. G372-381.
    Résumé : Fasting subjects were intragastrically intubated and received a coarsely emulsified test meal. Gastric aspirates were collected after 1, 2, 3, and 4 h. During digestion in the stomach, unemulsified lipids (> or = 100 microns) represented a minor fraction. A significant amount of the large 70- to 100-microns lipid droplets disappeared, and fine 1- to 10-microns droplets were generated. The median lipid droplet diameter significantly decreased (21.9 vs. 52.9 microns) after 1 h and kept intermediate values for longer periods of time. The emulsion surface area was 100-120 m2/l and was basically provided by 1- to 100-microns droplets. Lipolysis catalyzed by gastric lipase primarily occurred within the first hour of digestion (11.9%). Smaller droplets were enriched in triglyceride lipolytic products. The free fatty acid concentrations were in the range of 5.6-8.2 mM over 1-4 h. The present finding demonstrates for the first time that in the human stomach most dietary lipids are present in the form of emulsified droplets, in the range of 20-40 microns, and that gastric lipolysis can help to increase emulsification in the stomach.
    Mots-clés : Dietary Fats, Emulsions, Fats, Humans, Hydrogen-Ion Concentration, Lipase, Lipolysis, Stomach, Sucrose, Tissue Distribution, Triglycerides.
  • Borel, P, Armand, M, Pasquier, B, Senft, M, Dutot, G, Melin, C, Lafont, H & Lairon, D 1994, “Digestion and absorption of tube-feeding emulsions with different droplet sizes and compositions in the rat”, JPEN. Journal of parenteral and enteral nutrition, vol. 18, no. 6, p. 534-543.
    Résumé : Assimilation of lipid nutrients depends on the efficiency of emulsified fat hydrolysis by digestive lipases. As shown in vitro, the activity of preduodenal and pancreatic lipases is governed by the physicochemical properties of emulsions. Thus the aim of this study was to evaluate in the rat how emulsions are digested and assimilated depending on their droplet size or solute composition. Fasted rats were intragastrically tube fed emulsions with different median droplet sizes (0.6 microns, fine; 22 microns, coarse) or solute composition (0.8 microns, complex fine) containing 14C-triolein and 3H-cholesterol. Two and 5 hours after feeding, fat-droplet size was measured in gastric and duodenal contents, and lipids were radioactively quantified in different compartments. In the stomach, the droplet size of the fine emulsions significantly increased to values (13 microns to 24 microns) comparable with those of the coarse emulsion (35 microns to 36 microns). In the duodenum, the droplet sizes of the three emulsions were in the range of 14 microns to 33 microns. After 2 hours, gastric triglyceride hydrolysis was significantly higher with the fine than with the coarse emulsion and was lower with the complex fine emulsion. Gastric emptying of fat was significantly different, with the following decreasing order: coarse, fine, and complex fine emulsion. In the small intestine, the fine and coarse emulsions were processed comparably, whereas the assimilation of the fine complex emulsion was significantly delayed. Calculations indicate that ingested fatty acids were distributed in the peripheral tissues at different rates with the same decreasing order. The fate of a lipophilic nutrient, cholesterol, was also markedly altered by the type of emulsion. These data support the concept that tube-fed emulsions with different droplet sizes and solute composition are digested differently and thus are metabolized differently.
    Mots-clés : Absorption, Animals, Cholesterol, Chylomicrons, Dietary Fats, Digestion, Duodenum, Emulsions, Enteral Nutrition, Fatty Acids, Gastric Emptying, Liver, Male, Particle Size, Rats, Rats, Wistar, Stomach, Triglycerides, Triolein.
  • Dubois, C, Armand, M, Azais-Braesco, V, Portugal, H, Pauli, AM, Bernard, PM, Latgé, C, Lafont, H, Borel, P & Lairon, D 1994, “Effects of moderate amounts of emulsified dietary fat on postprandial lipemia and lipoproteins in normolipidemic adults”, The American Journal of Clinical Nutrition, vol. 60, no. 3, p. 374-382.
    Résumé : Eight normolipidemic males ingested a meal containing either 42 g fat or 31 g fat in the form of emulsions (9.0 and 9.2 m2) and a fixed amount of retinyl palmitate. Fasting and postmeal blood samples were obtained for 7 h. Serum and chylomicron triglyceride responses were related to the amount of fat ingested and peaked after 2-3 h. The chylomicron retinyl palmitate response was lower (P < or = 0.05) with the 31-g fat supply. After the 42-g fat intake, but not after the 31-g fat intake, serum free cholesterol and phospholipids increased and esterified cholesterol decreased postprandially. Significantly different responses were observed after both meals for low-density-lipoprotein (LDL) free cholesterol, very-low-density-lipoprotein (VLDL) and LDL esterified cholesterol, and high-density-lipoprotein (HDL) phospholipids. These data show that ingesting 31 g instead of 42 g fat in a meal reduces postmeal lipoprotein variations and suggest that a threshold level of dietary fat should be overcome to promote significant postprandial changes in lipoprotein particles.
    Mots-clés : Adult, Anticarcinogenic Agents, Cholesterol, Chylomicrons, Dietary Fats, Dose-Response Relationship, Drug, Double-Blind Method, Eating, Emulsions, Fasting, Humans, Insulin, Lipids, Lipoproteins, Male, Phospholipids, Triglycerides, Vitamin A.
  • Dubois, C, Armand, M, Mekki, N, Portugal, H, Pauli, AM, Bernard, PM, Lafont, H & Lairon, D 1994, “Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects”, Journal of Lipid Research, vol. 35, no. 11, p. 1993-2007.
    Résumé : Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.
    Mots-clés : Adult, Cholesterol, Cholesterol Esters, Cholesterol, Dietary, Food, Humans, Kinetics, Lipids, Lipoproteins, Lipoproteins, HDL, Lipoproteins, LDL, Lipoproteins, VLDL, Male, Triglycerides.


Journal Article
  • Dubois, C, Cara, L, Armand, M, Borel, P, Senft, M, Portugal, H, Pauli, AM, Bernard, PM, Lafont, H & Lairon, D 1993, “Effects of pea and soybean fibre on postprandial lipaemia and lipoproteins in healthy adults”, European Journal of Clinical Nutrition, vol. 47, no. 7, p. 508-520.
    Résumé : To evaluate some possible mechanisms whereby total dietary fibre (TDF) may affect lipid metabolism in humans, six normolipidaemic males ingested on separate days a low-fibre test meal (2.8 g TDF) containing 70 g fat and 756 mg cholesterol, enriched with 10 g TDF in the form of either pea fibre or soybean fibre. Fasting and post-meal blood samples were obtained for 7 h and chylomicrons (CM) were isolated. Lipoproteins (VLDL+CM remnants, LDL, HDL) were isolated from the baseline samples and the samples of the 2-3 h triglyceride peaks. As compared to the postprandial response given by the control low-fibre test meal, adding fibre induced no change in serum glucose, insulin or Apo A1 and Apo B variations. The serum triglyceride response was not altered by adding fibres but the 2-3 h chylomicron triglyceride rise was increased (P < or = 0.05) by soybean fibre. VLDL+CM remnants, LDL and HDL triglyceride variations were unchanged with fibres. Cholesterolaemia decreased postprandially for 6 h, and was further lowered in the presence of pea fibre. This resulted from a marked decrease in serum esterified cholesterol. The chylomicron cholesterol and phospholipid rise was lowered in the presence of either fibre. The postprandial changes in the free cholesterol concentrations of the various lipoprotein classes were not altered by fibre whereas changes from baseline in esterified cholesterol concentrations were reduced by soybean fibre in LDL and amplified by soybean and pea fibres in HDL. The results obtained show that dietary fibre present in legumes may alter postprandial lipaemia and lipoproteins in humans to a variable extent. These effects could be related to some long-term metabolic effects.
    Mots-clés : Adult, Blood Glucose, Cholesterol, Chylomicrons, Dietary Fiber, Double-Blind Method, Fabaceae, Humans, Insulin, Lipids, Lipoproteins, Male, Plants, Medicinal, Soybeans, Triglycerides.


Journal Article
  • Cara, L, Armand, M, Borel, P, Senft, M, Portugal, H, Pauli, AM, Lafont, H & Lairon, D 1992, “Long-term wheat germ intake beneficially affects plasma lipids and lipoproteins in hypercholesterolemic human subjects”, The Journal of Nutrition, vol. 122, no. 2, p. 317-326.
    Résumé : In previous short-term studies in rats and humans, the ingestion of raw wheat germ lowered plasma triglycerides and cholesterol. Thus, the present study was designed to investigate the possible long-term effects of wheat germ intake. Diet supplementation with raw wheat germ or partially defatted wheat germ was tested in two separate groups of 10 and 9 free-living human subjects, respectively. They all exhibited hypercholesterolemia (6.14-9.67 mmol/L cholesterol) and 11 had hypertriglyceridemia. None was diabetic. Fasting blood samples were taken at the beginning of the study, after 4 wk of 20 g/d wheat germ intake, after 14 additional weeks of 30 g/d wheat germ intake and after 12 wk without any supplementation. Dietary records were kept for seven and three consecutive days, before and during the wheat germ intake periods, respectively. Raw wheat germ intake significantly decreased plasma cholesterol (-8.7%) and tended to reduce VLDL cholesterol (-19.6%) after 4 wk. After 14 additional weeks, plasma cholesterol (-7.2%) and LDL cholesterol (-15.4%) remained lower and plasma triglycerides (-11.3%) tended to be lower. The apo B:apo A1 ratio significantly decreased after both periods. Partially defatted wheat germ transiently decreased plasma triglycerides and cholesterol after a 4-wk intake. The present data indicate that wheat germ reduces cholesterolemia in the long term and could play a beneficial role in the dietary management of type IIa and IIb hyperlipidemia.
    Mots-clés : Adult, Aged, Analysis of Variance, Apolipoproteins, Cholesterol, Female, Humans, Hypercholesterolemia, Lipoproteins, Male, Middle Aged, Triglycerides, Triticum.
  • Cara, L, Dubois, C, Borel, P, Armand, M, Senft, M, Portugal, H, Pauli, AM, Bernard, PM & Lairon, D 1992, “Effects of oat bran, rice bran, wheat fiber, and wheat germ on postprandial lipemia in healthy adults”, The American Journal of Clinical Nutrition, vol. 55, no. 1, p. 81-88.
    Résumé : Six normolipidemic males ingested on separate days a low-fiber test meal [2.8 g dietary fiber (TDF)] containing 70 g fat and 756 mg cholesterol, enriched or not with 10 g TDF as oat bran, rice bran, or wheat fiber or 4.2 g TDF as wheat germ. Fasting and postmeal blood samples were obtained for 7 h and chylomicrons were isolated. Adding fibers to the test meal induced no change in serum glucose or insulin responses. The serum triglyceride response was lower (P less than or equal to 0.05) in the presence of oat bran, wheat fiber, or wheat germ and chylomicron triglycerides were reduced with wheat fiber. All fiber sources reduced chylomicron cholesterol. Cholesterolemia decreased postprandially for 6 h and was further lowered in the presence of oat bran. Serum apolipoprotein (apo) A-1 and apo B concentrations were not affected. Thus, dietary fibers from cereals may reduce postprandial lipemia in humans to a variable extent.
    Mots-clés : Adult, Blood Glucose, Cereals, Cholesterol, Chylomicrons, Dietary Fiber, Double-Blind Method, Humans, Insulin, Lipids, Male, Oryza sativa, Random Allocation, Triglycerides, Triticum.


Journal Article
  • Borel, P, Armand, M, Senft, M, Andre, M, Lafont, H & Lairon, D 1991, “Gastric lipase: evidence of an adaptive response to dietary fat in the rabbit”, Gastroenterology, vol. 100, no. 6, p. 1582-1589.
    Résumé : In the rabbit, the stomach is the only source of preduodenal lipase, and in humans, it is quantitatively the most important. Thus, the adaptive response of gastric and pancreatic lipases to dietary fat was studied in the adult rabbit. Effect of duration was studied by feeding rabbits 12% dietary fat for 1, 2, or 4 weeks or 2.7% for 2 weeks (control). To study the effects of the amount of fat, rabbits were fed the control diet (2.7% fat) or 6% and 12% dietary fat for 2 weeks. The influence of sunflower oil and butter was compared by feeding rabbits 12% dietary fat for 2 weeks. Approximately doubling (6% vs. 2.7%) the usual amount of dietary fat was sufficient to induce a maximum increase in gastric lipase activity in the fundus [+ 66.3% (units per gram tissue) or + 85.2% (units per milligram protein)] and the total stomach mucosa [+ 84.5% (units per mucosa)], whereas pancreatic lipase activity only significantly increased when rabbits were fed 12% dietary fat. A full adaptive response was observed for both gastric and pancreatic lipases after 2 weeks of diet. Triglyceride composition did not noticeably change the adaptive response of both lipolytic enzymes. The present results agree closely with those concerning lingual lipase in the rat and evidence that gastric lipase shows an adaptive response to moderate fat intake. The implications of these findings concerning humans are discussed.
    Mots-clés : Adaptation, Physiological, Animals, Dietary Fats, Gastric Mucosa, Lipase, Male, Pancreas, Rabbits, Time Factors.
  • Cara, L, Borel, P, Armand, M, Senft, M, Lafont, H, Portugal, H, Pauli, AM, Boulze, D, Lacombe, C & Lairon, D 1991, “Plasma lipid lowering effects of wheat germ in hypercholesterolemic subjects”, Plant Foods for Human Nutrition (Dordrecht, Netherlands), vol. 41, no. 2, p. 135-150.
    Résumé : The present study was performed to investigate the possible effects of wheat germ supplementation on lipid metabolism in humans. Ten free-living adult subjects participated in the study. None was obese or diabetic. They all presented an hypercholesterolemia (from 6.58 to 9.50 mM), associated in 6 over 10 cases to an hypertriglyceridemia (from 1.70 to 5.00 mM). The subjects were studied in three consecutive periods, during which they first were on their usual diet (first week), they then ingested a daily supplement of 30 g wheat germ (4 weeks) and then they returned to their usual basal diet (4 weeks follow-up). Dietary records were obtained for 7 and 3 consecutive days before and during wheat germ supplementation, respectively. Fasting blood samples were taken at the end of each period. After 4 weeks of wheat germ intake, glycemia did not change while total plasma cholesterol significantly decreased (paired Student's t test, p less than or equal to 0.05) from 7.80 to 7.15 mM. LDL and HDL cholesterol values did not show marked changes, but VLDL cholesterol significantly dropped by 40.6%. Thus, the plasma/HDL total cholesterol ratio was significantly lower. Apoprotein B and A1 decreased. In the hypertriglyceridemic subjects, this was accompanied by a significant reduction of plasma triglycerides (1.64 vs. 2.68 mM) and a marked drop of VLDL triglycerides (-51%). Taken as a whole, the present results obtained in humans are very close to those previously obtained in the rat and point out that wheat germ may play a beneficial role in the dietary management of hyperlipidemia.
    Mots-clés : Adult, Aged, Cholesterol, Dietary Fiber, Female, Follow-Up Studies, Humans, Hypercholesterolemia, Male, Middle Aged, Triglycerides, Triticum.


Journal Article
  • Armand, M, Borel, P, Cara, L, Senft, M, Chautan, M, Lafont, H & Lairon, D 1990, “Adaptation of lingual lipase to dietary fat in rats”, The Journal of Nutrition, vol. 120, no. 10, p. 1148-1156.
    Résumé : To study the adaptive response of lingual lipase and pancreatic lipase to dietary fat, three sets of experiments were performed in adult male rats. In the first experiment, rats were fed for 3 wk a low fat diet (4.5% fat) or a 10, 20 or 30% fat diet. In the second, rats were fed a 4.5% fat diet for 4 wk or a 20% fat diet for 1, 2 or 4 wk. In the third, rats were fed for 3 wk a 10% fat diet with various sources of fat (lard, sunflower oil, olive oil, peanut oil, butter, soybean oil, corn oil or salmon oil). The results demonstrated that 10% dietary fat was sufficient to promote a maximum significant increase in lingual lipase activity (expressed in units/g tissue and in units/mg protein), whereas pancreatic lipase responded steadily to 20 and 30% fat diets. After 1 wk of feeding 20% dietary fat, both enzyme specific activities had reached their maximum values. The fatty acid composition of dietary triglyceride molecules (chain length, number and location of double bonds) had no specific effect on the adaptation of lingual lipase. The physiological implications of these findings are discussed in regard to the role of intragastric lipolysis in fat digestion.
    Mots-clés : Animals, Body Weight, Dietary Fats, Lipase, Lipolysis, Male, Organ Size, Pancreas, Pancreatin, Rats, Rats, Inbred Strains, Tongue.
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