Sex specific association of fatty acid binding protein 2 and microsomal triacylglycerol transfer protein variants with response to dietary lipid changes in the 3 mo medi rivage primary intervention study

Background: The dietary guidelines targeted at reducing cardiovascular risk lead to largely heterogeneous responses in which genetic determinants are largely involved. Objectives: We evaluated the effect of fatty acid binding protein 2 (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) \u96493G/T allelic variations on plasma lipid markers, at baseline and on the response to the 3-mo Medi-RIVAGE primary prevention study. Design: Subjects with moderate cardiovascular disease risk (n =3D 169) were advised to reduce total and saturated dietary fats and to increase intake of monounsaturated and polyunsaturated fats. They were genotyped for FABP2 Ala54Thr and MTTP \u96493G/T allelic variations, and plasma was processed for cardiovascular risk marker analyses. Results: At baseline, men and women homozygous for Thr54 presented a significant opposite profile for plasma oleic acid (18:1), triacylglycerol-rich lipoprotein (TRL) cholesterol, and TRL phospholipids. In addition, all Thr/Thr men presented higher 18:1 values than did women. For the MTTP \u96493G/T polymorphism, although all TT subjects presented high apolipoprotein B-48, a genotype x sex interaction was present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. The prudent diet clearly improved plasma lipid markers. FABP2 genotype did not interact much with the amplitude of the response. However, for MTTP polymorphism, men homozygous for the T allele displayed a significantly more pronounced response than did men carrying the G allele, which is particularly evident by their larger decrease in the Framingham score. Conclusions: These 2 polymorphic loci are thus differently associated with the baseline lipid markers as well as with the response to nutritional recommendations, but both presented a marked sex-specific profile, with the response to diet being particularly efficient in men homozygous for the MTTP \u96493T allele

Les Isoformes intestinales et hépatiques des "fatty acid binding proteins" dans le trafic intracellulaire des acides gras et leur expression dans un modèle animal de syndrome métabolique

La consommation excessive de graisses est aujourd hui l une des causes principales de l augmentation de la prévalence des maladies métaboliques. Après leur hydrolyse, les graisses sont absorbées par les entérocytes sous forme d acides gras (AG) et de monoglycérides qui sont pris en charge dans la cellule par de petites protéines cytosoliques, les FABPs. L entérocyte exprime la I- FABP et la L-FABP dont la fonction spécifique dans le trafic intracellulaire des AG est toujours mal connue. Pour appréhender les relations structure-fonction in vivo, la caractérisation immunocytochimique de cellules Cos-1 transfectées exprimant de grandes quantités de FABPs a été réalisée. Ces protéines ciblent l AG vers des sites de métabolisation (mitochondries ou réticulum endoplasmique / appareil de Golgi). Lorsque chaque protéine est exprimée isolément dans la cellule, elle distribue de façon spécifique un analogue fluorescent d AG, suggérant une fonction propre pour chacune. Mais lorsqu elles sont toutes deux présentes, elles coopèrent pour la distribution de l AG dans des régions comparables à celles ciblées par la seule I-FABP suggérant un rôle de sensor pour cette protéine. Ce travail a été poursuivi en montrant que les régulations de l expression de la I-FABP et de la L-FABP différaient dans un modèle de syndrome métabolique induit par un régime riche en fructose chez le rat. Dans ce modèle, nous avons aussi analysé les effets de l apport dans le régime des AG polyinsaturés oméga 3 sur l expression de gènes impliqués dans le métabolisme énergétique et l inflammation. Un rôle spécifique de PPAR delta dans le foie et le cœur a pu être mis en évidence.AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocSudocFranceF

Effects of omega-3 fatty acids on gene expression in the fructose fed rat, a model of metabolic syndrome

National audienc

Hyperglycinemia in a 5-Week-Old Boy with Pulmonary Arterial Hypertension

International audienc

Gender-specific association of FABP2 and MTP variants with response to dietary lipid changes in the 3-mo Medi-RIVAGE primary intervention study

National audienc

Sex-specific association of fatty acid binding protein 2 and microsomal triacylglycerol transfer protein variants with response to dietary lipid changes in the 3-mo Medi-RIVAGE primary intervention study

International audienceBackground: The dietary guidelines targeted at reducing cardiovascular risk lead to largely heterogeneous responses in which genetic determinants are largely involved. Objectives: We evaluated the effect of fatty acid binding protein 2 (FABP2) Ala54Thr and microsomal triacylglycerol transfer protein (MTTP) –493G/T allelic variations on plasma lipid markers, at baseline and on the response to the 3-mo Medi-RIVAGE primary prevention study. Design: Subjects with moderate cardiovascular disease risk (n = 169) were advised to reduce total and saturated dietary fats and to increase intake of monounsaturated and polyunsaturated fats. They were genotyped for FABP2 Ala54Thr and MTTP –493G/T allelic variations, and plasma was processed for cardiovascular risk marker analyses. Results: At baseline, men and women homozygous for Thr54 presented a significant opposite profile for plasma oleic acid (18:1), triacylglycerol-rich lipoprotein (TRL) cholesterol, and TRL phospholipids. In addition, all Thr/Thr men presented higher 18:1 values than did women. For the MTTP –493G/T polymorphism, although all TT subjects presented high apolipoprotein B-48, a genotype x sex interaction was present for palmitic acid, linolenic acid, eicosatrienoic acid, and insulin. The prudent diet clearly improved plasma lipid markers. FABP2 genotype did not interact much with the amplitude of the response. However, for MTTP polymorphism, men homozygous for the T allele displayed a significantly more pronounced response than did men carrying the G allele, which is particularly evident by their larger decrease in the Framingham score. Conclusions: These 2 polymorphic loci are thus differently associated with the baseline lipid markers as well as with the response to nutritional recommendations, but both presented a marked sex-specific profile, with the response to diet being particularly efficient in men homozygous for the MTTP –493T allel

Gender-specific association of FABP2 and MTP variants with response to dietary lipid changes in the 3-mo Medi-RIVAGE primary intervention study

International audienc

Nutrigenetics: links between genetic background and response to Mediterranean-type diets

International audienceObjective It has been substantiated that the onset of most major diseases (CVD, diabetes, obesity, cancers, etc.) is modulated by the interaction between genetic traits (susceptibility) and environmental factors, especially diet. We aim to report more specific observations relating the effects of Mediterranean-type diets on cardiovascular risk factors and the genetic background of subjects. Results and conclusions In the first part, general concepts about nutrigenetics are briefly presented. Human genome has, overall, only marginally changed since its origin but it is thought that minor changes (polymorphisms) of common genes that occurred during evolution are now widespread in human populations, and can alter metabolic pathways and response to diets. In the second part, we report the data obtained during the Medi-RIVAGE intervention study performed in the South-East of France. Data obtained in 169 subjects at moderate cardiovascular risk after a 3-month dietary intervention indicate that some of the twenty-three single nucleotide polymorphisms (SNP) studied exhibit interactions with diets regarding changes of particular parameters after 3-month regimens. Detailed examples are presented, such as interactions between SNP in genes coding for microsomial transfer protein (MTTP) or intestinal fatty acid binding protein (FABP2) and triglyceride, LDL-cholesterol or Framigham score lowering in responses to Mediterranean-type diets. The data provided add further evidence of the interaction between particular SNP and metabolic responses to diets. Finally, improvement in dietary recommendations by taking into account known genetic variability has been discusse

Adenosine Concentration in Patients With Neurally Mediated Syncope

International audienceBackground Either high or low values of adenosine blood level (ABL) can differentiate some forms of neurally mediated syncope (NMS). A rapid method of measurement has recently been developed. The aim of the present study was: (1) to compare ABLs in an unselected population of consecutive patients referred for evaluation of suspected NMS syncope and in healthy controls; and (2) to assess the relative prevalence of low and high adenosine forms among an unselected syncope population. Method Whole blood was collected after finger puncture, blood being deposit on a blot paper and adenosine concentration was measured by liquid chromatography/mass spectrometry (LC-MS/MS). Results Among 89 control subjects, the median ABL value was 0.54 μM (IQR, 0.46–0.65). The lowest 5% and the upper 95% percentile were 0.40 and 0.80 μM, respectively. Compared with healthy subjects, the 146 patients with syncope showed, on average, a higher median ABL value [0.63 (IQR 0.45–0.73, p = 0.04)] and a larger distribution of values. Low ABL values below the 5th percentile were observed in 28 (19%) patients, and, in five controls, p = 0.003 and high ABL values were observed in 26 (18%) patients and five controls, p = 0.009. Conclusions ABL is different in patients with suspected NMS than in healthy subjects. Patients with low and high adenosine values account for 19% and 18% of the general population. Thus, low and high ABL limits, as defined in this study, may help to define the purinergic profile of unselected subjects with a clinical diagnosis of suspected NMS