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Title: The APOB -516C/T polymorphism is associated with differences in insulin sensitivity in healthy males during the consumption of diets with different fat content

Author
item PEREZ-MARTINEZ, PABLO - UNIV OF REINA SOFIA, ES
item PEREZ-JIMENEZ, FRANCISCO - UNIV OF REINA SOFIA, ES
item Ordovas, Jose
item MORENO, JUAN - UNIV OF REINA SOFIA, ES
item MORENO, RAFAEL - UNIV OF REINA SOFIA, ES
item FUENTES, FRANCISCO - UNIV OF REINA SOFIA, ES
item RUANO, JUAN - UNIV OF REINA SOFIA, ES
item GOMEZ, PURIFICACION - UNIV OF REINA SOFIA, ES
item MARIN, CARMEN - UNIV OF REINA SOFIA, ES
item LOPEZ-MIRANDA, JOSE - UNIV OF REINA SOFIA, ES

Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/10/2006
Publication Date: 3/9/2007
Citation: Perez-Martinez, P., Perez-Jimenez, F., Ordovas, J.M., Moreno, J.A., Moreno, R., Fuentes, F., Ruano, J., Gomez, P., Marin, C., Lopez-Miranda, J. 2007. The APOB -516C/T polymorphism is associated with differences in insulin sensitivity in healthy males during the consumption of diets with different fat content. British Journal of Nutrition. 97(4):622-627.

Interpretive Summary: Diabetes is a disorder of the body's metabolism, the process of converting the food we eat into energy. Insulin is the major factor in this process, which begins when food is broken down during digestion to create glucose, the main source of fuel for the body. Previous studies suggest that the effect of the APOB variants on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism. Change in dietary patterns may be key factor for development of insulin resistance (IR) and diabetes; however, genetic factors are also very important to predispose people to diabetes. We have examined the APOB gene in relation to susceptibility to insulin resistance in response to a high saturated fat-rich diet, followed by a carbohydrate-rich diet or a monounsaturated fat-rich diet following a randomized crossover design in a group of 59 white males. Our findings show that carriers of one form of the gene are more susceptible to IR than the others when the carriers consumed a high saturated fat-rich, low-carbohydrate diet. This suggests that is more important for the carriers of this form of the APOB gene to seek a healthier diet to prevent IR and eventually diabetes.

Technical Abstract: Several apo B polymorphic sites have been studied for their potential use as markers for CHD in the population and for potential gene-diet interactions. Our aim was to determine whether the presence of the -516C/T polymorphism in the APOB gene promoter modifies insulin sensitivity to dietary fat. We studied fifty-nine healthy volunteers (thirty men and twenty-nine women, thirty-six homozygotes for the -516C allele (C/C) (nineteen males and seventeen females) and twenty-three heterozygotes for the -516T allele (C/T) (eleven males and twelve females)). Subjects consumed three diets during the feeding study, 4 weeks each: an SFA-rich diet (38 % fat, 20 % SFA), followed by a carbohydrate (CHO)-rich diet (30 % fat, 55 % CHO) or a MUFA-rich diet (38 % fat, 22 % MUFA) following a randomised cross-over design. For each diet, we investigated peripheral insulin sensitivity with the insulin suppression test. Male carriers of the -516T allele showed a significantly greater decrease in steady-state plasma glucose concentrations when changing from the SFA-rich diet (9.18 (sd 1.35) mmol/l) to the MUFA (6.55 (sd 0.74) mmol/l) or the CHO (6.31 (sd 0.93) mmol/l) diets than did those who were homozygous for the C allele (P = 0.040). Furthermore, C/T subjects presented higher plasma NEFA values after consumption of the SFA diet compared with the MUFA and CHO diets (P = 0.001). This effect was not observed in females (P = 0.908). Our findings show that male carriers of the -516T allele, C/T, have a significant increase in insulin resistance after consumption of all diets, but the difference is more exaggerated after the SFA diet compared with the MUFA- and CHO-rich diets.