DataSheet_1.pdf

Abstract

Dietary intervention is a common tactic employed in attempt to curtail the current obesity epidemic. Changes in nutritional status alter metabolic hormones such as insulin or leptin, as well as the insulin-like growth factor (IGF) system. However, little is known about how metabolic parameters modified in overweight/obese subjects are restored after weight loss and if these changes differ between the sexes, especially regarding the IGF system. Here male and female mice received a high fat diet (HFD) or normal rodent chow for 8 weeks. Thereafter, half of the HFD mice were changed to chow (HFDCH) for an additional 4 weeks and the rest continued their assigned diet. Both sexes gained weight (p < 0.001) and increased their energy intake (p < 0.001) on the HFD, with these parameters normalizing after switching to chow but at different rates in males and females. Basal glycemia was increased (p < 0.05) by HFD in both sexes and recovered in HFDCH mice. Although both males and females had abnormal glucose tolerance tests (p < 0.001) that normalized in HFDCH mice, males were more affected. Insulin levels and HOMA index (p < 0.01) increased on the HFD in both sexes, but only males normalized this parameter when returned to chow. Dietary change normalized circulating leptin (p < 0.001), total IGF1 (p < 0.001), IGF2 (p < 0.001, only in females) and IGFBP3 (p < 0.001), which were increased after HFD, whereas free IGF1 levels remained elevated (p < 0.01). In both sexes hypothalamic mRNA levels of NPY and AgRP decreased on HFD (p < 0.001) and POMC increased (p < 0.001), with all normalizing in HFDCH mice, whereas the HFD-induced decrease in ObR remained so after dietary change (p < 0.05). Thus, weight loss on a healthy diet was associated with improvement of most metabolic parameters analyzed. However, in both sexes fIGF1 levels remained elevated, as did HOMA and insulin levels in females, and hypothalamic ObR remained decreased suggesting that these factors may require more time to normalize and that they could be involved in an increased adverse response to resumption of poor dietary habits.