Maternal High-Fat–High-Carbohydrate Diet-Induced Obesity Is Associated with Increased Appetite in Peripubertal Male but Not Female C57Bl/6J Mice

Diet-induced maternal obesity might play a critical role in altering hypothalamic development, predisposing the offspring to obesity and metabolic disease later in life. The objective of this study was to describe both phenotypic and molecular sex differences in peripubertal offspring energy homeostasis, using a mouse model of maternal obesity induced by a high-fat–high-carbohydrate (HFHC) diet. We report that males, not females, exposed to a maternal HFHC diet had increased energy intake. Males exposed to a maternal HFHC diet had a 15% increased meal size and a 46% increased frequency, compared to the control (CON) males, without a change in energy expenditure. CON and HFHC offspring did not differ in body weight, composition, or plasma metabolic profile. HFHC diet caused decreased hypothalamic glucocorticoid expression, which was further decreased in males compared to females. Maternal weight, maternal caloric intake, and male offspring meal frequency were inversely correlated with offspring hypothalamic insulin receptor (IR) expression. There was a significant interaction between maternal-diet exposure and sex in hypothalamic IR. Based on our preclinical data, we suggest that interventions focusing on normalizing maternal nutrition might be considered to attenuate nutritional influences on obesity programming and curb the continuing rise in obesity rates.