Background: Obesity prevalence is growing in our population. Twin studies have estimated the heritability of dietary intakes to about 30%. The objective of this study was to verify whether polymorphisms in genes involved in fatty acid metabolism are associated with dietary fat intakes. Methods: Seven hundred participants were recruited. A validated food frequency questionnaire was used to assess dietary intakes. PCR-RFLP and TAQMAN methodology were used to genotype PPAR α Leu162Val, PPAR γ Pro12Ala, PPAR δ –87T>C, PPARGC1 α Gly482Ser, FASN Val1483Ile and SREBF1 c.*619C>G. Statistical analyses were executed with SAS statistical package. Results: Carriers of the Ala12 allele of PPAR γ Pro12Ala polymorphism had higher intakes of total fat (p = 0.04). For FASN Val1483Ile polymorphism, significant gene-sex interaction effects were found for total fat and saturated fat intakes (p = 0.02 and p = 0.002, respectively). No significant difference in fat intakes was observed for PPAR α Leu162Val, PPAR δ –87T>C, PPARGC1 α Gly482Ser and SREBF1 c.*619C>G polymorphisms. Conclusions: Polymorphisms in PPAR γ and FASN seem to be associated with dietary fat intakes. Genetic variants are important to take into account when studying dietary intakes.

Statistique Canada: L’obésité chez les adultes au Canada. 2008.
Wyatt SB, Winters KP, Dubbert PM: Overweight and obesity: prevalence, consequences, and causes of a growing public health problem. Am J Med Sci 2006;331:166–174.
Bell CG, Walley AJ, Froguel P: The genetics of human obesity. Nat Rev Genet 2005;6:221–234.
Melanson EL, Astrup A, Donahoo WT: The relationship between dietary fat and fatty acid intake and body weight, diabetes, and the metabolic syndrome. Ann Nutr Metab 2009;55:229–243.
Elmadfa I, Kornsteiner M: Fats and fatty acid requirements for adults. Ann Nutr Metab 2009;55:56–75.
Choquette AC, Lemieux S, Tremblay A, Chagnon YC, Bouchard C, Vohl MC, et al: Evidence of a quantitative trait locus for energy and macronutrient intakes on chromosome 3q27.3: the Quebec Family Study. Am J Clin Nutr 2008;88:1142–1148.
Hasselbalch AL, Heitmann BL, Kyvik KO, Sorensen TI: Studies of twins indicate that genetics influence dietary intake. J Nutr 2008;138:2406–2412.
Hur YM, Bouchard TJ Jr, Eckert E: Genetic and environmental influences on self-reported diet: a reared-apart twin study. Physiol Behav 1998;64:629–636.
van BM, van Nieuwenhoven FA: PPARs as therapeutic targets in cardiovascular disease. Expert Opin Ther Targets 2010;14:1029–1045.
Evans RM, Barish GD, Wang YX: PPARs and the complex journey to obesity. Nat Med 2004;10:355–361.
Hihi AK, Michalik L, Wahli W: PPARs: transcriptional effectors of fatty acids and their derivatives. Cell Mol Life Sci 2002;59:790–798.
Xu HE, Lambert MH, Montana VG, Parks DJ, Blanchard SG, Brown PJ, et al: Molecular recognition of fatty acids by peroxisome proliferator-activated receptors. Mol Cell 1999;3:397–403.
Fernandez-Alvarez A, Alvarez MS, Gonzalez R, Cucarella C, Muntane J, Casado M: Human SREBP1c expression in liver is directly regulated by peroxisome proliferator-activated receptor alpha (PPARalpha). J Biol Chem 2011;286:21466–21477.
Duval C, Muller M, Kersten S: PPARalpha and dyslipidemia. Biochim Biophys Acta 2007;1771:961–971.
Schwartz GJ, Fu J, Astarita G, Li X, Gaetani S, Campolongo P, et al: The lipid messenger OEA links dietary fat intake to satiety. Cell Metab 2008;8:281–288.
Fu J, DiPatrizio NV, Guijarro A, Schwartz GJ, Li X, Gaetani S, et al: Sympathetic activity controls fat-induced oleoylethanolamide signaling in small intestine. J Neurosci 2011;31:5730–5736.
Vohl MC, Lepage P, Gaudet D, Brewer CG, Betard C, Perron P, et al: Molecular scanning of the human PPARα gene: association of the L162v mutation with hyperapobetalipoproteinemia. J Lipid Res 2000;41:945–952.
Rudkowska I, Caron-Dorval D, Verreault M, Couture P, Deshaies Y, Barbier O, et al: PPARalpha L162V polymorphism alters the potential of n-3 fatty acids to increase lipoprotein lipase activity. Mol Nutr Food Res 2010;54:543–550.
Robitaille J, Brouillette C, Houde A, Lemieux S, Perusse L, Tchernof A, et al: Association between the PPARalpha-L162V polymorphism and components of the metabolic syndrome. J Hum Genet 2004;49:482–489.
Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM: mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 1994;8:1224–1234.
Masugi J, Tamori Y, Mori H, Koike T, Kasuga M: Inhibitory effect of a proline-to-alanine substitution at codon 12 of peroxisome proliferator-activated receptor-gamma 2 on thiazolidinedione-induced adipogenesis. Biochem Biophys Res Commun 2000;268:178–182.
Deeb SS, Fajas L, Nemoto M, Pihlajamaki J, Mykkanen L, Kuusisto J, et al: A Pro12Ala substitution in PPARgamma2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 1998;20:284–287.
Lu M, Sarruf DA, Talukdar S, Sharma S, Li P, Bandyopadhyay G, et al: Brain PPAR-gamma promotes obesity and is required for the insulin-sensitizing effect of thiazolidinediones. Nat Med 2011;17:618–622.
Perreault M, Will S, Panza D, Gareski T, Harding K, Kubasiak D, et al: Modulation of nutrient sensing nuclear hormone receptors promotes weight loss through appetite suppression in mice. Diabetes Obes Metab 2010;12:234–245.
Barish GD, Narkar VA, Evans RM: PPAR delta: a dagger in the heart of the metabolic syndrome. J Clin Invest 2006;116:590–597.
Harrington WW, Britt S, Wilson G, Milliken O, Binz G, Lobe C, et al: The Effect of PPARalpha, PPARdelta, PPARgamma, and PPARpan Agonists on Body Weight, Body Mass, and Serum Lipid Profiles in Diet-Induced Obese AKR/J Mice. PPAR Res 2007;2007:97125.
Skogsberg J, Kannisto K, Cassel TN, Hamsten A, Eriksson P, Ehrenborg E: Evidence that peroxisome proliferator-activated receptor delta influences cholesterol metabolism in men. Arterioscler Thromb Vasc Biol 2003;23:637–643.
Puigserver P, Spiegelman BM: Peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1 alpha): transcriptional coactivator and metabolic regulator. Endocr Rev 2003;24:78–90.
Esterbauer H, Oberkofler H, Krempler F, Patsch W: Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression. Genomics 1999;62:98–102.
Miura S, Kai Y, Kamei Y, Ezaki O: Isoform-specific increases in murine skeletal muscle peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha) mRNA in response to beta2-adrenergic receptor activation and exercise. Endocrinology 2008;149:4527–4533.
Ma D, Li S, Lucas EK, Cowell RM, Lin JD: Neuronal inactivation of peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha) protects mice from diet-induced obesity and leads to degenerative lesions. J Biol Chem 2010;285:39087–39095.
Yang Y, Mo X, Chen S, Lu X, Gu D: Association of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PPARGC1A) gene polymorphisms and type 2 diabetes mellitus: a meta-analysis. Diabetes Metab Res Rev 2011;27:177–184.
Esterbauer H, Oberkofler H, Linnemayr V, Iglseder B, Hedegger M, Wolfsgruber P, et al: Peroxisome proliferator-activated receptor-gamma coactivator-1 gene locus: associations with obesity indices in middle-aged women. Diabetes 2002;51:1281–1286.
Ridderstrale M, Johansson LE, Rastam L, Lindblad U: Increased risk of obesity associated with the variant allele of the PPARGC1A Gly482Ser polymorphism in physically inactive elderly men. Diabetologia 2006;49:496–500.
Barroso I, Luan J, Sandhu MS, Franks PW, Crowley V, Schafer AJ, et al: Meta-analysis of the Gly482Ser variant in PPARGC1A in type 2 diabetes and related phenotypes. Diabetologia 2006;49:501–505.
Stumvoll M, Fritsche A, t’Hart LM, Machann J, Thamer C, Tschritter O, et al: The Gly482Ser variant in the peroxisome proliferator-activated receptor gamma coactivator-1 is not associated with diabetes-related traits in non-diabetic German and Dutch populations. Exp Clin Endocrinol Diabetes 2004;112:253–257.
Chen S, Yan W, Huang J, Yang W, Gu D: Peroxisome proliferator-activated receptor-gamma coactivator-1alpha polymorphism is not associated with essential hypertension and type 2 diabetes mellitus in Chinese population. Hypertens Res 2004;27:813–820.
Nitz I, Ewert A, Klapper M, Doring F: Analysis of PGC-1alpha variants Gly482Ser and Thr612Met concerning their PPARgamma2-coactivation function. Biochem Biophys Res Commun 2007;353:481–486.
Choi YS, Hong JM, Lim S, Ko KS, Pak YK: Impaired coactivator activity of the Gly482 variant of peroxisome proliferator-activated receptor gamma coactivator-1alpha (PGC-1alpha) on mitochondrial transcription factor A (Tfam) promoter. Biochem Biophys Res Commun 2006;344:708–712.
Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, et al: Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 1999;98:115–124.
Semenkovich CF: Regulation of fatty acid synthase (FAS). Prog Lipid Res 1997;36:43–53.
Franck N, Gummesson A, Jernas M, Glad C, Svensson PA, Guillot G, et al: Identification of adipocyte genes regulated by caloric intake. J Clin Endocrinol Metab 2011;96:E413–E418.
Berndt J, Kovacs P, Ruschke K, Kloting N, Fasshauer M, Schon MR, et al: Fatty acid synthase gene expression in human adipose tissue: association with obesity and type 2 diabetes. Diabetologia 2007;50:1472–1480.
Loftus TM, Jaworsky DE, Frehywot GL, Townsend CA, Ronnett GV, Lane MD, et al: Reduced food intake and body weight in mice treated with fatty acid synthase inhibitors. Science 2000;288:2379–2381.
Tu Y, Thupari JN, Kim EK, Pinn ML, Moran TH, Ronnett GV, et al: C75 alters central and peripheral gene expression to reduce food intake and increase energy expenditure. Endocrinology 2005;146:486–493.
Kovacs P, Harper I, Hanson RL, Infante AM, Bogardus C, Tataranni PA, et al: A novel missense substitution (Val1483Ile) in the fatty acid synthase gene (FAS) is associated with percentage of body fat and substrate oxidation rates in nondiabetic Pima Indians. Diabetes 2004;53:1915–1919.
Schleinitz D, Kloting N, Korner A, Berndt J, Reichenbacher M, Tonjes A, et al: Effect of genetic variation in the human fatty acid synthase gene (FASN) on obesity and fat depot-specific mRNA expression. Obesity (Silver Spring) 2010;18:1218–1225.
Moreno-Navarrete JM, Botas P, Valdes S, Ortega FJ, Delgado E, Vazquez-Martin A, et al: Val1483Ile in FASN gene is linked to central obesity and insulin sensitivity in adult white men. Obesity (Silver Spring) 2009;17:1755–1761.
Horton JD, Goldstein JL, Brown MS: SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver. J Clin Invest 2002;109:1125–1131.
Shimomura I, Shimano H, Horton JD, Goldstein JL, Brown MS: Differential expression of exons 1a and 1c in mRNAs for sterol regulatory element binding protein-1 in human and mouse organs and cultured cells. J Clin Invest 1997;99:838–845.
Shimano H: SREBPs: physiology and pathophysiology of the SREBP family. FEBS J 2009;276:616–621.
Shimano H: Sterol regulatory element-binding protein family as global regulators of lipid synthetic genes in energy metabolism. Vitam Horm 2002;65:167–194.
Grarup N, Stender-Petersen KL, Andersson EA, Jorgensen T, Borch-Johnsen K, Sandbaek A, et al: Association of variants in the sterol regulatory element-binding factor 1 (SREBF1) gene with type 2 diabetes, glycemia, and insulin resistance: a study of 15,734 Danish subjects. Diabetes 2008;57:1136–1142.
Paradis AM, Godin G, Perusse L, Vohl MC: Associations between dietary patterns and obesity phenotypes. Int J Obes (Lond) 2009;33:1419–1426.
Goulet J, Nadeau G, Lapointe A, Lamarche B, Lemieux S: Validity and reproducibility of an interviewer-administered food frequency questionnaire for healthy French-Canadian men and women. Nutr J 2004;3:13.
Yen CJ, Beamer BA, Negri C, Silver K, Brown KA, Yarnall DP, et al: Molecular scanning of the human peroxisome proliferator activated receptor gamma (hPPAR gamma) gene in diabetic Caucasians: identification of a Pro12Ala PPAR gamma 2 missense mutation. Biochem Biophys Res Commun 1997;241:270–274.
Livak KJ: Allelic discrimination using fluorogenic probes and the 5′ nuclease assay. Genet Anal 1999;14:143–149.
Robitaille J, Despres JP, Perusse L, Vohl MC: The PPAR-gamma P12A polymorphism modulates the relationship between dietary fat intake and components of the metabolic syndrome: results from the Quebec Family Study. Clin Genet 2003;63:109–116.
Robitaille J, Gaudet D, Perusse L, Vohl MC: Features of the metabolic syndrome are modulated by an interaction between the peroxisome proliferator-activated receptor-delta –87T>C polymorphism and dietary fat in French-Canadians. Int J Obes (Lond) 2007;31:411–417.
Felder TK, Oberkofler H, Weitgasser R, Mackevics V, Krempler F, Paulweber B, et al: The SREBF-1 locus is associated with type 2 diabetes and plasma adiponectin levels in a middle-aged Austrian population. Int J Obes (Lond) 2007;31:1099–1103.
Bouchard-Mercier A, Godin G, Lamarche B, Perusse L, Vohl MC: Effects of peroxisome proliferator-activated receptors, dietary fat intakes and gene-diet interactions on peak particle diameters of low-density lipoproteins. J Nutrigenet Nutrigenomics 2011;4:36–48.
Kallen CB, Lazar MA: Antidiabetic thiazolidinediones inhibit leptin (ob) gene expression in 3T3-L1 adipocytes. Proc Natl Acad Sci USA 1996;93:5793–5796.
Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, et al: Role of leptin in the neuroendocrine response to fasting. Nature 1996;382:250–252.
Ryan KK, Li B, Grayson BE, Matter EK, Woods SC, Seeley RJ: A role for central nervous system PPAR-gamma in the regulation of energy balance. Nat Med 2011;17:623–626.
Chen K, Li F, Li J, Cai H, Strom S, Bisello A, et al: Induction of leptin resistance through direct interaction of C-reactive protein with leptin. Nat Med 2006;12:425–432.
Evans D, Mann WA, de HJ, Michel U, Wendt D, Kortner B, et al: Variation in the gene for human peroxisome proliferator activated receptor gamma (PPARgamma) does not play a major role in the development of morbid obesity. Int J Obes Relat Metab Disord 2000;24:647–651.
Ereqat S, Nasereddin A, Azmi K, Abdeen Z, Amin R: Impact of the Pro12Ala Polymorphism of the PPAR-Gamma 2 Gene on Metabolic and Clinical Characteristics in the Palestinian Type 2 Diabetic Patients. PPAR Res 2009;2009:874126.
Ahluwalia M, Evans M, Morris K, Currie C, Davies S, Rees A, et al: The influence of the Pro12Ala mutation of the PPAR-gamma receptor gene on metabolic and clinical characteristics in treatment-naive patients with type 2 diabetes. Diabetes Obes Metab 2002;4:376–378.
Anderson AL, Harris TB, Houston DK, Tylavsky FA, Lee JS, Sellmeyer DE, et al: Relationships of dietary patterns with body composition in older adults differ by gender and PPAR-gamma Pro12Ala genotype. Eur J Nutr 2010;49:385–394.
Adamo KB, Dent R, Langefeld CD, Cox M, Williams K, Carrick KM, et al: Peroxisome proliferator-activated receptor gamma 2 and acyl-CoA synthetase 5 polymorphisms influence diet response. Obesity (Silver Spring) 2007;15:1068–1075.
Memisoglu A, Hu FB, Hankinson SE, Manson JE, De V, I, Willett WC, et al: Interaction between a peroxisome proliferator-activated receptor gamma gene polymorphism and dietary fat intake in relation to body mass. Hum Mol Genet 2003;12:2923–2929.
Luan J, Browne PO, Harding AH, Halsall DJ, O’Rahilly S, Chatterjee VK, et al: Evidence for gene-nutrient interaction at the PPARgamma locus. Diabetes 2001;50:686–689.
Franks PW, Jablonski KA, Delahanty L, Hanson RL, Kahn SE, Altshuler D, et al: The Pro12Ala variant at the peroxisome proliferator-activated receptor gamma gene and change in obesity-related traits in the Diabetes Prevention Program. Diabetologia 2007;50:2451–2460.
Vaccaro O, Lapice E, Monticelli A, Giacchetti M, Castaldo I, Galasso R, et al: Pro12Ala polymorphism of the PPARgamma2 locus modulates the relationship between energy intake and body weight in type 2 diabetic patients. Diabetes Care 2007;30:1156–1161.
Lagou V, Scott RA, Manios Y, Chen TL, Wang G, Grammatikaki E, et al: Impact of peroxisome proliferator-activated receptors gamma and delta on adiposity in toddlers and preschoolers in the GENESIS Study. Obesity (Silver Spring) 2008;16:913–918.
Dedoussis GV, Manios Y, Kourlaba G, Kanoni S, Lagou V, Butler J, et al: An age-dependent diet-modified effect of the PPARgamma Pro12Ala polymorphism in children. Metabolism 2011;60:467–473.
Kim EK, Miller I, Landree LE, Borisy-Rudin FF, Brown P, Tihan T, et al: Expression of FAS within hypothalamic neurons: a model for decreased food intake after C75 treatment. Am J Physiol Endocrinol Metab 2002;283:E867–E879.
Arsenijevic D, de BF, Plamondon J, Paradis E, Vallet P, Richard D, et al: Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice. J Cereb Blood Flow Metab 2006;26:433–445.
Jguirim-Souissi I, Jelassi A, Hrira Y, Najah M, Slimani A, Addad F, et al: +294T/C polymorphism in the PPAR-delta gene is associated with risk of coronary artery disease in normolipidemic Tunisians. Genet Mol Res 2010;9:1326–1333.
Aberle J, Hopfer I, Beil FU, Seedorf U: Association of the T+294C polymorphism in PPAR delta with low HDL cholesterol and coronary heart disease risk in women. Int J Med Sci 2006;3:108–111.
Eberle D, Clement K, Meyre D, Sahbatou M, Vaxillaire M, Le GA, et al: SREBF-1 gene polymorphisms are associated with obesity and type 2 diabetes in French obese and diabetic cohorts. Diabetes 2004;53:2153–2157.
Black AE, Goldberg GR, Jebb SA, Livingstone MB, Cole TJ, Prentice AM: Critical evaluation of energy intake data using fundamental principles of energy physiology: 2. Evaluating the results of published surveys. Eur J Clin Nutr 1991;45:583–599.
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