title: The -514 C/T polymorphism in the hepatic lipase gene promoter is associated with insulin sensitivity in a healthy young population.
abstract: Impaired insulin action has been associated with diabetes, dyslipidemia and atherosclerotic vascular disease. The expression of insulin resistance results from the interaction of environmental and genetic factors. Human hepatic lipase (HL) is a lipolytic enzyme that plays a role in the metabolism of several lipoproteins, while insulin up-regulates the activity of HL via insulin-responsive elements in the HL promoter. We have examined the influence of -514 C/T polymorphism in the hepatic lipase gene promoter on insulin sensitivity in 59 healthy young subjects (30 males and 29 females). The volunteers were subjected to three dietary periods, each lasting four weeks. During the first period all subjects consumed a saturated fat (SFA)-enriched diet with 38% as fat (20% SFA, 12% monounsaturated fatty acids (MUFA) and 6% polyunsaturated fatty acids (PUFA)). In the second and third dietary periods, a randomized crossover design was used, consisting of a low fat, high carbohydrate diet (CHO diet) (< 10% SFA, 12% MUFA and 6% PUFA) and a high-MUFA, or Mediterranean diet, with < 10% SFA, 22% MUFA and 6% PUFA. We determined the in vivo insulin resistance using the insulin suppression test with somatostatin. Steady-state plasma glucose (SSPG) concentrations (a measure of insulin sensitivity) were significantly higher in men carriers of the -514T allele after the consumption of the SFA diet than after the CHO diet and the Mediterranean diet. This effect was not observed in women. Moreover, there were no significant differences in insulin sensitivity after the three diets in men and women with the CC genotype. In summary, our results show an improvement in insulin sensitivity in men with the -514T allele of the HL promoter polymorphism, when MUFA and carbohydrates are consumed instead of SFA fat.
authors.affiliation: Unit of Lipids and Arteriosclerosis, Hospital Universitario Reina Sofia, 14004 Córdoba, Spain.
authors.forename: Purificación
authors.initials: P
authors.lastname: Gómez
authors.forename: Francisco
authors.initials: F
authors.lastname: Pérez-Jiménez
authors.forename: Carmen
authors.initials: C
authors.lastname: Marín
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Moreno
authors.forename: María José
authors.initials: MJ
authors.lastname: Gómez
authors.forename: Cecilia
authors.initials: C
authors.lastname: Bellido
authors.forename: Pablo
authors.initials: P
authors.lastname: Pérez-Martínez
authors.forename: Francisco
authors.initials: F
authors.lastname: Fuentes
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Paniagua
authors.forename: José
authors.initials: J
authors.lastname: López-Miranda
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D018592:Cross-Over Studies; D004032:Diet; D004041:Dietary Fats / Q000008:administration & dosage* / Q000378:metabolism; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005838:Genotype; D006801:Humans; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008049:Lipase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; C504173:LIPC protein, human; D008049:Lipase