Intake of trans fatty acid-rich hydrogenated fat during pregnancy and lactation inhibits the hypophagic effect of central insulin in the adult offspring

Abstract

Objective: Using rats we examined whether maternal intake of hydrogenated fat rich in trans fatty acids affects brain fatty acid profile, hypothalamic content of insulin receptor and insulin receptor substrate-1 proteins, and the hypophagic effect of centrally administered insulin in 3-mo-old male progeny.

Methods: Throughout pregnancy and lactation, Wistar rats ate isocaloric/normolipidic diets with soybean oil (control) or soybean oil-derived hydrogenated fat (trans diet) as a fat source. Upon weaning, the trans offspring continued on the trans diet (trans group) or were switched to a control diet (trans-control group).

Results: Compared with control rats, trans rats had lower brain levels of eicosapentaenoic acid. Compared with trans rats, trans-control rats had increased levels of total polyunsaturated fatty acids and arachidonic acid and decreased levels of trans fatty acids, saturated fatty acids, and monounsaturated fatty acids. Insulin receptor and insulin receptor substrate-1 levels were significantly lower (44% and 38%, respectively) in trans than in control rats. In trans-control rats, insulin receptor was 26% lower (P < 0.05), whereas insulin receptor substrate-1 was 50% lower, than in control rats. Insulin decreased 24-h feeding in control (27%) and trans (38%) rats but failed to do so in trans-control rats. The latter group had increased serum glucose levels.

Conclusions: The data suggest that the early (intrauterine/perinatal) exposure to hydrogenated fat rich in trans fatty acids programmed the hypothalamic feeding control mechanisms. As young adults, only trans-control animals showed loss of insulin-induced hypophagia, indicating that the mismatch between early and later nutritional environments was relevant. However, the trans group also showed signs of altered appetite signaling mechanisms, suggesting that the early adaptations may have deleterious consequences later in life.