Effet du polymorphisme PPARα-L162V sur la réponse lipidique à une supplémentation en acides gras polyinsaturés oméga-3

Le projet de recherche sous forme d’intervention nutritionnelle dont fait l’objet ce mémoire de maîtrise avait pour principal objectif de comparer la réponse lipidique à une supplémentation en acides gras polyinsaturés oméga-3 chez des porteurs et des non-porteurs du polymorphisme PPAR L162V. Quatorze hommes porteurs et quatorze non-porteurs du polymorphisme PPAR L162V ont été appariés pour l’âge et l’indice de masse corporelle. Chaque sujet recevait une supplémentation quotidienne en acides gras oméga-3 de 5g d’huile de poissons, et ce, pour une durée de six semaines. Avant l’intervention, les variables anthropométriques et les concentrations de lipoprotéines/lipides n’étaient pas associées au polymorphisme. Indépendamment du génotype, la supplémentation en acides gras oméga-3 fut reliée à la diminution significative des taux de triglycérides plasmatiques, de la concentration de glucose à jeun, de la pression artérielle diastolique et finalement de l’augmentation du taux d’apolipoprotéine B. Une interaction gène-diète significative a également été observée pour la protéine C-réactive . Les résultats de cette étude suggèrent que des variations du gène PPAR puissent contribuer à la variabilité interindividuelle des concentrations plasmatiques de la protéine C-réactive en réponse aux acides gras polyinsaturés oméga-3.The main objective of this master degree project was to examine whether omega-3 polyunsaturated fatty acids induced changes in cardiovascular disease risks factors are influenced by the PPAR L162V polymorphism. A total of 14 men carriers of the V162 allele and 14 L162 homozygotes were matched according to age and body mass index. All men were supplemented daily with 5g of fish oil during a 6-week period. At screening, both genotype groups were similar for anthropometric indices and plasma lipoprotein/lipid concentrations. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triglyceride and fasting glucose concentrations, diastolic blood pressure and with an increase in total Apolipoprotein B concentrations. A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations. The PPAR L162V polymorphism may contribute to the interindividual variability in the cardiovascular disease risk factor response to omega-3 polyunsaturated fatty acids

PPARaplha L162V polymorphism alters the potential of N-3 fatty acids to increase lipoprotein lipase activity

Omega‐3 fatty acids (FAs) may accelerate plasma triglyceride (TG) clearance by altering lipoprotein lipase (LPL) activity. Yet, the ability of n‐3 FAs to increase LPL activity is dependent on transcription factors such as peroxisome proliferator‐activated receptor alpha (PPARα). The objective was to examine the effects of n‐3 FAs on LPL activity considering the occurrence of PPAR α L162V polymorphism. First, 14 pairs of men either L162 homozygotes or carriers of the V162 allele were supplemented with n‐3 FAs. Second, transient transfections in HepG2 cells, for the L162‐ and V162‐PPARα variants with the peroxisome proliferator‐response element from the human LPL gene, were transactivated with n‐3 FAs. In vivo results demonstrate that the LPL activity increased non‐significantly by 14.4% in L162 homozygotes compared with 6.6% in carriers of the PPAR α‐V162 allele, after n‐3 FA supplementation. Additionally, the L162 homozygotes tended towards an inverse correlation between LPL activities and plasma TG levels. Conversely, carriers of the V162 allele showed no such relationship. In vitro data demonstrates that transcription rates of LPL tended to be higher for the L162‐PPARα than V162‐PPARα after n‐3 FAs activation. Overall, these results indicate that n‐3 FA supplementation increases the transcription rate of LPL to a greater extent in L162‐PPARα than V162‐PPARα

Effect of the PPAR-Alpha L162V polymorphism on the cardiovascular disease risk factor in response to n–3 polyunsaturated fatty acids

Background: Dietary n–3 polyunsaturated fatty acids (PUFAs) decrease the risk of cardiovascular disease (CVD). Yet, genetic variations of the gene encoding the peroxisome proliferator-activated receptor- (PPAR ) can also modulate CVD risk factors. Since fatty acids, including n–3 PUFAs, are natural ligands of PPAR , a gene-diet interaction effect could be observed. Aims: To examine whether n–3 PUFAinduced changes in CVD risk factors are influenced by the PPAR L162V polymorphism. Methods: Fourteen men, carriers of the V162 allele and 14 L162 homozygotes, were matched according to age and body mass index. Subjects followed, for 8 weeks, a low-fat diet and then were supplemented daily with 5 g of fish oil for 6 weeks. Results: Baseline characteristics were similar for both genotype groups. Independently of the genotype, the supplementation was associated with a significant decrease in plasma triacylglycerol and fasting glucose concentrations, diastolic blood pressure, and with an increase in total apolipoprotein B concentrations. The extent of the decrease in plasma triacylglycerol concentrations was comparable for both genotype groups (p ! 0.03). A significant genotype-by-diet interaction effect was observed for plasma C-reactive protein concentrations (p = 0.01). Conclusions: The PPAR L162V polymorphism may contribute to the interindividual variability in the CVD risk factor response to n–3 PUFAs

Specific appetite, energetic and metabolomics responses to fat overfeeding in resistant-to-bodyweight-gain constitutional thinness

Supplementary information available for this article at http://www.nature.com/nutd/journal/v4/n7/suppinfo/nutd201417s1.htmlBACKGROUND: Contrasting with obesity, constitutional thinness (CT) is a rare condition of natural low bodyweight. CT exhibits preserved menstruation in females, no biological marker of undernutrition, no eating disorders but a bodyweight gain desire. Anorexigenic hormonal profile with high peptide tyrosine tyrosine (PYY) was shown in circadian profile. CT could be considered as the opposite of obesity, where some patients appear to resist diet-induced bodyweight loss.OBJECTIVE: The objective of this study was to evaluate appetite regulatory hormones in CTs in an inverse paradigm of diet-induced weight loss.METHODS: A 4-week fat overfeeding (2640 kJ excess) was performed to compare eight CT women (body mass index (BMI) < 17.5 kg m(-2)) to eight female controls (BMI 18.5-25 k gm(-2)). Appetite regulatory hormones profile after test meal, food intake, bodyweight, body composition, energy expenditure and urine metabolomics profiles were monitored before and after overfeeding.RESULTS: After overfeeding, fasting total and acylated ghrelin were significantly lower in CTs than in controls (P = 0.01 and 0.03, respectively). After overfeeding, peptide tyrosine tyrosine (PYY) and glucagon-like-peptide 1 both presented earlier (T15 min vs T30 min) and higher post-meal responses (incremental area under the curve) in CTs compared with controls. CTs failed to increase bodyweight (+0.22 +/- 0.18 kg, P = 0.26 vs baseline), contrasting with controls (+0.72 +/- 0.26 kg, P = 0.03 vs baseline, P = 0.01 vs CTs). Resting energy expenditure increased in CTs only (P = 0.031 vs baseline). After overfeeding, a significant negative difference between total energy expenditure and food intake was noticed in CTs only (-2754 +/- 720 kJ, P = 0.01).CONCLUSION: CTs showed specific adaptation to fat overfeeding: overall increase in anorexigenic hormonal profile, enhanced post prandial GLP-1 and PYY and inverse to controls changes in urine metabolomics. Overfeeding revealed a paradoxical positive energy balance contemporary to a lack of bodyweight gain, suggesting yet unknown specific energy expenditure pathways in CTs