Brigitte Laillet | Institut National de la Recherche Agronomique (original) (raw)

Papers by Brigitte Laillet

Fundamental & Clinical Pharmacology, 2011

n-3 polyunsatured fatty acids (PUFA), better known as omega-3, are essential for normal growth, d... more n-3 polyunsatured fatty acids (PUFA), better known as omega-3, are essential for normal growth, development, and function of many organ systems. Prospective epidemiological studies show an inverse relation between fish intake/elevated PUFA consumption and mortality from coronary heart disease [1-4], which is attributed to a reduced risk of sudden cardiac death [5] and/or anti-arrhythmic effect of PUFA [6-10]. Moreover, in experimental models, high dietary fish oil prevents hypertension [11,12] and vascular dysfunction [13,14]. These protective cardiac and vascular effects are thought to involve a decrease in oxidative stress, due to a decrease in pro-oxydant systems [15,16] and/or increase in antioxidant systems [17,18], but other mechanism(s) such as

Background: Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin re... more Background: Saturated fatty acid-rich high fat (HF) diets trigger abdominal adiposity, insulin resistance, type 2 diabetes and cardiac dysfunction. This study was aimed at evaluating the effects of nascent obesity on the cardiac function of animals fed a high-fat diet and at analyzing the mechanisms by which these alterations occurred at the level of coronary reserve. Materials and methods: Rats were fed a control (C) or a HF diet containing high proportions of saturated fatty acids for 3 months. Thereafter, their cardiac function was evaluated in vivo using a pressure probe inserted into the cavity of the left ventricle. Their heart was isolated, perfused iso-volumetrically according to the Langendorff mode and the coronary reserve was evaluated by determining the endothelial-dependent (EDV) and endothelial-independent (EIV) vasodilatations in the absence and presence of endothelial nitric oxide synthase and cyclooxygenase inhibitors (L-NAME and indomethacin). The fatty acid composition of cardiac phospholipids was then evaluated. Results: Although all the HF-fed rats increased their abdominal adiposity, some of them did not gain body weight (HF-group) compared to the C group whereas other ones had a higher body weight (HF+). All HF rats displayed a higher in vivo cardiac activity associated with an increased EDV. In the HF-group, the improved EDV was due to an increase in the endothelial cell vasodilatation activity whereas in the HF+ group, the enhanced EDV resulted from an improved sensitivity of coronary smooth muscle cells to nitric oxide. Furthermore, in the HF-group the main pathway implicated in the EDV was the NOS pathway while in the HF+ group the COX pathway. Conclusions: Nascent obesity-induced improvement of cardiac function may be supported by an enhanced coronary reserve occurring via different mechanisms. These mechanisms implicate either the endothelial cells activity or the smooth muscle cells sensitivity depending on the body adiposity of the animals.

Since few decades, incidence of obesity and type 2 diabetes (T2D) is increasing. Excessive intake... more Since few decades, incidence of obesity and type 2 diabetes (T2D) is increasing. Excessive intake of energy leads to fat overload and formation of lipotoxic compounds mainly derived from the saturated fatty acid palmitate in insulin-sensitive tissues (muscle, liver and white adipose tissue), promoting insulin resistance (IR, a well-known metabolic disorder in T2D). Supplementation with n-3 fatty acids (n-3FA) is suggested to reduce lipotoxicity and IR. We hypothesized that, according to the n-3FA used, differential and specific effects on palmitate metabolism in muscle cells will be demonstrated. C2C12 myotubes were treated with 500 µM of palmitate without or with 50 µM of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for 16 hours and collected for measurement of membrane fluidity using diphenyl-hexatriene, ceramide content, insulin-dependent Akt protein phosphorylation (as an index of IR). The assessment of the intracellular metabolism and in...

Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, ... more Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD,…) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that a long-term docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle mass in vivo. Six-wk-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h. The effect of DHA on i) muscle energy stores (glycogen, triglycerides (TG)), ii) muscle mass, and iii) Akt and AMPK signaling pathways involved in the control of protein and energy metabolism has been addressed. The regulation of the formation and the fate of lipid stores has been also evaluated. Feeding mice a DHA-enriched diet prior to fasting elevated muscle glycogen contents without any change in TG levels, reduced muscle wasting, blocked the 55 % decrease in Akt phosphorylation, and reduced by 30-40% the activation of AMPK, ubiquitination o...

Journal of Clinical Lipidology, 2018

alter miRNA binding sites in the FADS1 3 0 UTR. In HuH7 and HepG2 cells transfected with FADS1 3 ... more alter miRNA binding sites in the FADS1 3 0 UTR. In HuH7 and HepG2 cells transfected with FADS1 3 0 UTR luciferase vectors, the haplotype constructs bearing the rs174546T minor allele showed 30% less luciferase activity. This relative decrease reached 60% in the presence of miR-149-5p and was partly abolished by cotransfection with an miR-149-5p inhibitor. CONCLUSION: This study identifies FADS1 rs174546 as a functional variant that may explain the associations between FADS1-FADS2 polymorphisms and lipid-related phenotypes.

Journal of Neurogastroenterology and Motility, 2017

Background/Aims Human gut microbiota harbors numerous metabolic properties essential for the host... more Background/Aims Human gut microbiota harbors numerous metabolic properties essential for the host's health. Increased intestinal transit time affects a part of the population and is notably observed with human aging, which also corresponds to modifications of the gut microbiota. Thus we tested the metabolic and compositional changes of a human gut microbiota induced by an increased transit time simulated in vitro. Methods The in vitro system, Environmental Control System for Intestinal Microbiota, was used to simulate the environmental conditions of 3 different anatomical parts of the human colon in a continuous process. The retention times of the chemostat conditions were established to correspond to a typical transit time of 48 hours next increased to 96 hours. The bacterial communities, short chain fatty acids and metabolite fingerprints were determined. Results Increase of transit time resulted in a decrease of biomass and of diversity in the more distal compartments. Short chain fatty acid analyses and metabolite fingerprinting revealed increased activity corresponding to carbohydrate fermentation in the proximal compartments while protein fermentations were increased in the lower parts. Conclusions This study provides the evidence that the increase of transit time, independently of other factors, affects the composition and metabolism of the gut microbiota. The transit time is one of the factors that explain some of the modifications seen in the gut microbiota of the elderly, as well as patients with slow transit time.

Journal of Lipid Research, 2016

Metabolic syndrome (MetS) is defined as a cluster of several risk factors for type 2 diabetes and... more Metabolic syndrome (MetS) is defined as a cluster of several risk factors for type 2 diabetes and cardiovascular diseases (1, 2). MetS is closely related to the progression of insulin resistance (IR) and the accumulation of fat mass, notably in the visceral area (2). Thus, alteration in the cross-talk between key metabolic tissues, such as the liver, adipose tissue (AT), skeletal muscle, and intrinsic dysfunctions in these organs probably represent a key step in the progression of MetS (3, 4). The impairment of lipid storage capacity in subcutaneous AT has been related to the alteration of the endocrine function of the tissue, the increased free FA release in the circulation, visceral fat accumulation (5), and the deposition of ectopic fat in other organs contributing to IR (6). Lifestyle changes are recommended for the prevention and the management of MetS. Several reports from the literature have suggested that metabolic abnormalities and alterations of AT biology could be prevented by increasing the intake of n-3 PUFAs (7). n-3 PUFAs, especially those of marine origin (i.e., C20:5n-3, EPA and C22:6n-3, DHA), were identified as potent positive regulators of insulin sensitivity in vitro (8) and in animal models (9). However, epidemiological studies aiming at determining the beneficial effects of those n-3 PUFAs and their common precursor alpha linolenic acid (C18:3n-3, ALA), led to inconclusive results (10). This may be mainly due to the fact that different experimental protocols were used for Abstract The impact of alpha linolenic acid (ALA), EPA, and DHA on obesity and metabolic complications was studied in mice fed a high-fat, high-sucrose (HF) diet. HF diets were supplemented with ALA, EPA, or DHA (1% w/w) and given to C57BL/6J mice for 16 weeks and to Ob/Ob mice for 6 weeks. In C57BL/6J mice, EPA reduced plasma cholesterol (20%), limited fat mass accumulation (23%) and adipose cell hypertrophy (50%), and reduced plasma leptin concentration (60%) compared with HF-fed mice. Furthermore, mice supplemented with EPA exhibited a higher insulin sensitivity (+24%) and glucose tolerance (+20%) compared with HF-fed mice. Similar effects were observed in EPA-supplemented Ob/Ob mice, although fat mass accumulation was not prevented. By contrast, in comparison with HF-fed mice, DHA did not prevent fat mass accumulation, increased plasma leptin concentration (+128%) in C57BL/6J mice, and did not improve glucose homeostasis in C57BL/6J and Ob/Ob mice. In 3T3-L1 adipocytes, DHA stimulated leptin expression whereas EPA induced adiponectin expression, suggesting that improved leptin/adiponectin balance may contribute to the protective effect of EPA. In conclusion, supplementation with EPA, but not ALA and DHA, could preserve glucose homeostasis in an obesogenic environment and limit fat mass accumulation in the early stage of weight gain.

Journal of Cachexia, Sarcopenia and Muscle, 2016

Background Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney... more Background Muscle wasting prevails in numerous diseases (e.g. diabetes, cardiovascular and kidney diseases, COPD,…) and increases healthcare costs. A major clinical issue is to devise new strategies preventing muscle wasting. We hypothesized that 8-week docosahexaenoic acid (DHA) supplementation prior to fasting may preserve muscle mass in vivo. Methods Six-week-old C57BL/6 mice were fed a DHA-enriched or a control diet for 8 weeks and then fasted for 48 h. Results Feeding mice a DHA-enriched diet prior to fasting elevated muscle glycogen contents, reduced muscle wasting, blocked the 55% decrease in Akt phosphorylation, and reduced by 30-40% the activation of AMPK, ubiquitination, or autophagy. The DHA-enriched diet fully abolished the fasting induced-messenger RNA (mRNA) over-expression of the endocannabinoid receptor-1. Finally, DHA prevented or modulated the fasting-dependent increase in muscle mRNA levels for Rab18, PLD1, and perilipins, which determine the formation and fate of lipid droplets, in parallel with muscle sparing. Conclusions These data suggest that 8-week DHA supplementation increased energy stores that can be efficiently mobilized, and thus preserved muscle mass in response to fasting through the regulation of Akt-and AMPK-dependent signalling pathways for reducing proteolysis activation. Whether a nutritional strategy aiming at increasing energy status may shorten recovery periods in clinical settings remains to be tested.

American Journal of Physiology - Endocrinology And Metabolism, 2015

Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modificat... more Decline in skeletal muscle mass and function starts during adulthood. Among the causes, modifications of the mitochondrial function could be of major importance. Polyunsaturated fatty (ω-3) acids have been shown to play a role in intracellular functions. We hypothesize that docosahexaenoic acid (DHA) supplementation could improve muscle mitochondrial function that could contribute to limit the early consequences of aging on adult muscle. Twelve-month-old male Wistar rats were fed a low-polyunsaturated fat diet and were given DHA (DHA group) or placebo (control group) for 9 wk. Rats from the DHA group showed a higher endurance capacity (+56%, P < 0.05) compared with control animals. Permeabilized myofibers from soleus muscle showed higher O2 consumptions ( P < 0.05) in the DHA group compared with the control group, with glutamate-malate as substrates, both in basal conditions (i.e., state 2) and under maximal conditions (i.e., state 3, using ADP), along with a higher apparent K...

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2016

Excessive energy intake leads to fat overload and the formation of lipotoxic compounds mainly der... more Excessive energy intake leads to fat overload and the formation of lipotoxic compounds mainly derived from the saturated fatty acid palmitate (PAL), thus promoting insulin resistance (IR) in skeletal muscle. N-3 polyunsaturated fatty acids (n-3PUFA) may prevent lipotoxicity and IR. The purpose of this study was to examine the differential effects of n-3PUFA on fatty acid metabolism and insulin sensitivity in muscle cells. C2C12 myotubes were treated with 500μM of PAL without or with 50μM of alpha-linolenic acid (ALA), eicosapentaenoic acid (EPA) or docosahexaenoic acid (DHA) for 16h. PAL decreased insulin-dependent AKT activation and glucose uptake and increased the synthesis of ceramides and diglycerides (DG) derivatives, leading to protein kinase Cθ activation. EPA and DHA, but not ALA, prevented PAL-decreased AKT activation but glucose uptake was restored to control values by all n-3PUFA vs. PAL. Total DG and ceramide contents were decreased by all n-3PUFA, but only EPA and DHA increased PAL β-oxidation, decreased PAL incorporation into DG and reduced protein kinase Cθ activation. EPA and DHA emerge as better candidates than ALA to improve fatty acid metabolism in skeletal muscle cells, notably via their ability to increase mitochondrial β-oxidation.

Journal of Physiology and Biochemistry, 2015

Abdominal obesity increases the incidence of cardiac events but reduces mortality when one of the... more Abdominal obesity increases the incidence of cardiac events but reduces mortality when one of these events occurs. The phenomenon called obesity paradox might be related to myocardial energetics. This study was aimed at determining whether long-term abdominal adiposity alters cardiac energy function. Two groups of male Wistar rats were fed a standard or a Western-type (WD) diet for 8 months. The ex vivo coronary reactivity and mechanical function as well as the mitochondrial oxidative phosphorylation (mOxPhos) and hydrogen peroxide release (mH2O2r) were determined. Abdominal adiposity was augmented by the WD. This was also the case for the coronary reactivity to acetylcholine, but the rate pressure product remained roughly stable despite a reduction of the left ventricle-developed pressure partly compensated by a slight increase in heart rate. The prolonged WD administration resulted in an improvement of mOxPhos, but the mH2O2r was exaggerated which was confirmed in the whole cell by a reduced aconitase to fumarase ratio. This did not modify the plasma oxidative stress due to an increased plasma antioxidant status. In conclusion, long-term WD administration improved the cardiac fitness and might predispose the organism to the obesity paradox. Conversely, the increased mitochondrial mH2O2r can precipitate the heart toward cardiomyopathy if the WD is maintained for a longer duration.

Nutrition Clinique et Métabolisme, 2014

Effets de l'exercice maternel sur l'homéostasie du glucose et la fonction pancréatique de la desc... more Effets de l'exercice maternel sur l'homéostasie du glucose et la fonction pancréatique de la descendance à l'âge de 3 semaines et 7 mois

Nutrition Clinique et Métabolisme, 2014

un changement de régime pendant 1 mois (J60) : la margarine est remplacée par l'huile de sardine ... more un changement de régime pendant 1 mois (J60) : la margarine est remplacée par l'huile de sardine et vice versa. Résultats et Analyse statistique.-À J60 versus J30, le remplacement de l'huile de sardine par la margarine augmente les teneurs en cholestérol des lipoprotéines de très faible densité (C-VLDL) de 12 % et de faible densité (C-LDL) de 13 % mais réduit le C-HDL 2 et C-HDL 3 (lipoprotéines de haute densité) de 34 % et 15 %, respectivement. L'évaluation de la peroxydation lipidique montre que les teneurs en substances réactives à l'acide thiobarbiturique (TBARS) sont augmentées au niveau du sérum (+43 %) et des fractions LDL-HDL 1 (+26 %) et HDL 2 et HDL 3 (+41 %). De même, les valeurs des isoprostanes sériques sont élevées (+37 %). Toutefois, les teneurs en hydroperoxydes sont abaissées de 14 % et l'activité enzymatique de la PON1 reste inchangée. Lorsque la margarine est remplacée par l'huile de sardine, les teneurs en C-VLDL et C-LDL sont réduites de 30 % et 37 %, respectivement, alors que celles des HDL 2 et HDL 3 sont respectivement augmentées (-10 % et-51 %). Par ailleurs, les teneurs en TBARS et en hydroperoxydes sont respectivement diminuées au niveau du sérum (-33 % et-18 %) et des LDL-HDL 1 (-þ7 %), HDL 2 (-þ28 %) et HDL 3 (-þ14 %). De même, les isoprostanes sont abaissés (-þ31 %). En revanche, une augmentation significative de l'activité de la PON1 est notée (+74 %). Conclusion.-Chez le rat obèse, le remplacement de l'huile de sardine par la margarine augmente la peroxydation lipidique au niveau du sérum et des lipoprotéines et ne semble pas influencer l'activité antioxydante de la PON1. En revanche, la substitution de la margarine par l'huile de sardine atténue efficacement la peroxydation lipidique et stimule l'activité antioxydante de la PON1, ce qui est en faveur d'une réduction du risque cardiovasculaire. P155 Le DHA restore la sensibilité musculaire à l'insuline en inhibant l'activation de la PKC-theta par les céramides

Nutrition Clinique et Métabolisme, 2014

In the aquatic environment biology and hydrology should assist each other in explaining the estab... more In the aquatic environment biology and hydrology should assist each other in explaining the establishment, fluctuation, and limitation of the aquatic vegetation. However, the description of running and still waters by hydrology and habitat hydraulics, and the description of the aquatic vegetation, and its dynamics, rarely lead to results on a comparable scale. This is due to some intrinsic methodological features of both sciences, but also due to the fact that there is not much effort to find a common basis of scale. This is to no surprise because most of the time a hydrologist, and vice versa a biologist, tries to solve problems on his own, rarely calling for a partner from the other field. In the personal view of a biologist aspects are pointed out which may lead to a better interpretation of biological processes through habitat-related hydrological and/or hydraulic assessments. The terms macrophytes, environment and success are defined first. The function of macrophytes as a part of the aquatic ecosystem is explained, and related to important environmental factors. Examples are given for water flow as the most prominent abiotic factor. With respect to water flow and light the assessment of these parameters should be more detailed regarding space and time to be relevant to the scales in which aquatic plant life takes place. With regard to nutrient assessment spatial resolution is not as sensitive an issue as long as the water body, and not the interstitial, is concerned. However, any increase in detail will considerably raise the effort, and the cost, of data acquisition. Measuring plant "success" with physiological methods and biometrics can be too complicated for in situ work. Methods fitted to single species spatial development may cope with such problems and GIS is the tool to choose in such cases. Finally the urgent need to find common scales among hydrologists and biologists is addressed.

The Journal of Nutritional Biochemistry, 2015

Skeletal muscle plays a major role in the control of whole body glucose disposal in response to i... more Skeletal muscle plays a major role in the control of whole body glucose disposal in response to insulin stimulus. Excessive supply of fatty acids to this tissue triggers cellular and molecular disturbances leading to lipotoxicity, inflammation, mitochondrial dysfunctions, impaired insulin response and decreased glucose uptake. This study was conducted to analyze the preventive effect of docosahexaenoic acid (DHA), a long-chain polyunsaturated n-3 fatty acid, against insulin resistance, lipotoxicity and inflammation in skeletal muscle at doses compatible with nutritional supplementation. DHA (30 μM) prevented insulin resistance in C2C12 myotubes exposed to palmitate (500 μM) by decreasing protein kinase C (PKC)-θ activation and restoring cellular acylcarnitine profile, insulin-dependent AKT phosphorylation and glucose uptake. Furthermore, DHA protected C2C12 myotubes from palmitate-or lipopolysaccharide-induced increase in Ptgs2, interleukin 6 and tumor necrosis factor-α mRNA level, probably through the inhibition of p38 MAP kinase and c-Jun amino-terminal kinase. In LDLR −/− mice fed a high-cholesterol-high-sucrose diet, supplementation with DHA reaching up to 2% of daily energy intake enhanced the insulin-dependent AKT phosphorylation and reduced the PKC-θ activation in skeletal muscle. Therefore, DHA used at physiological doses participates in the regulation of muscle lipid and glucose metabolisms by preventing lipotoxicity and inflammation.

European journal of clinical nutrition, Jan 22, 2014

Background/Objectives:The omega-3 index (the summed percentage content of eicosapentaenoic and do... more Background/Objectives:The omega-3 index (the summed percentage content of eicosapentaenoic and docosahexaenoic acids in red blood cells) is associated with a lower risk of fatal coronary heart disease and sudden cardiac death. We aimed to determine which socio-demographic, behavioural or clinical factors are independently associated with the omega-3 index and the extent to which seafood consumption mediates the index's association with socio-economic status (SES).Subjects/Methods:As part of the cross-sectional MONA LISA-NUT survey (2005-2007), gas chromatography was used to analyse the red blood cell fatty acid composition in 503 French subjects aged 35-64 years. Dietary data were collected by trained dieticians via a validated food frequency questionnaire and a prospective 3-day food record. Risk factors were estimated with standardised measurements and questionnaires. SES was assessed through the self-reported educational and income tax levels.Results:The mean±s.d. omega-3 ind...

British Journal of Nutrition, 2011

Long-chain (LC)n-3 PUFA have a broad range of biological properties that can be achieved at the g... more Long-chain (LC)n-3 PUFA have a broad range of biological properties that can be achieved at the gene expression level. This has been well described in liver, where LCn-3 PUFA modulate the expression of genes related to lipid metabolism. However, the complexity of biological pathway modulations and the nature of bioactive molecules are still under investigation. The present study aimed to investigate the dose–response effects of LCn-3 PUFA on the production of peroxidised metabolites, as potential bioactive molecules, and on global gene expression in liver. Hypercholesterolaemic rabbits received by daily oral administration (7 weeks) either oleic acid-rich oil or a mixture of oils providing 0·1, 0·5 or 1 % (groups 1, 2 and 3 respectively) of energy as DHA. Levels of specific peroxidised metabolites, namely 4-hydroxyhexenal (4-HHE)–protein adducts, issued from LCn-3 PUFA were measured by GC/MS/MS in liver in parallel to transcription profiling. The intake of LCn-3 PUFA increased, in a...

Journal of Lipid Research, 2009

male mice is associated with a specifi c loss of ABCA1 and an increase in apoptosis of apical cel... more male mice is associated with a specifi c loss of ABCA1 and an increase in apoptosis of apical cells of the proximal caput epididymidis. ATP-binding cassette G1 (ABCG1) and scavenger receptor B1 (SR-B1), two other cholesterol transporters, show little if any modifi cations. Our study also revealed that SR-B1 appears to have a peculiar expression pattern along the epididymal duct. These results should help in understanding the functional roles of LXR in cholesterol traffi cking processes in caput epididymidis.-Ouvrier, A., R.

Fundamental & Clinical Pharmacology, 2011

Journal of Clinical Lipidology, 2018

Journal of Neurogastroenterology and Motility, 2017

Journal of Lipid Research, 2016

Journal of Cachexia, Sarcopenia and Muscle, 2016

American Journal of Physiology - Endocrinology And Metabolism, 2015

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, 2016

Journal of Physiology and Biochemistry, 2015

Nutrition Clinique et Métabolisme, 2014

The Journal of Nutritional Biochemistry, 2015

European journal of clinical nutrition, Jan 22, 2014

British Journal of Nutrition, 2011

Journal of Lipid Research, 2009