Sex and Age Affect Food Choice and Metabolic Adaptation to Short-Term High-Calorie Palatable Diet Consumption in Mice

The incidence of severe obesity is increasing among young people and depends on gender. The development of obesity is promoted by the consumption of high-calorie palatable foods, yet the influence of age and gender on adaptation to high-calorie diets remain poorly understood. The aim of this study was to investigate the effect of sex and age on short-term adaptation to a high-calorie palatable diet (PD, standard chow, lard, and sweet cookie) in the age range from youth to adulthood in mice. Male and female C57Bl/6J mice were fed the PD for 2 weeks, starting at ages 7 (young), 17 (early adult), and 27 weeks (adult). Energy intake, food choice, as well as morphometric and plasma biochemical parameters were evaluated. Both sex and age significantly affected food choices and all studied parameters. From the young to the early adult age, blood levels of fibroblast growth factor 21 (FGF21) decreased, while cookie consumption increased. The PD increased white fat mass and blood glucose levels, while reducing glucose tolerance in young females more markedly than in young males. In early adult mice, the PD had no effect on glucose tolerance or blood glucose levels. In adult mice, the PD increased body weight, induced hyperleptinemia, hyperglycemia, hyperinsulinemia, and reduced glucose tolerance only in males, with no such effects observed in females. Thus, the response to a high-calorie diet changes with age and differs by sex: male mice are more resilient to a PD than females in their youth but less so in adulthood. Sex and the age at which a diet is initiated are critical factors in the pathophysiology of obesity.