Sex-specific effects of prepubertal stress and high-fat diet on leptin signaling in rats

Both stress exposure and high-fat diet (HFD) are contributors to the alarming prevalence of obesity. Leptin is secreted from adipose tissue and regulates appetite and body weight via the JAK-STAT3 pathway in the hypothalamus; it also regulates the hypothalamic-pituitary-thyroid axis, modulating energy homeostasis. Leptin signaling may be impaired by HFD intake, and here we investigate whether social isolation during the prepubertal period, associated with chronic HFD, can exert long-term effects on metabolic parameters in a sex-specific manner.

Wistar male and female rats were divided into two groups (receiving standard chow or standard chow and HFD), which were subdivided into (1) exposed to social isolation during the prepubertal period or (2) not exposed.

HFD induced sex-specific effects on leptin signaling and on the hypothalamic-pituitary-thyroid axis; males receiving HFD presented increased T4 but a reduced T3:T4 ratio and higher caloric efficiency during development. A stress × diet interaction was noted for leptin signaling in males, where pSTAT3 was higher when these factors were applied together. On the other hand, females were more susceptible to early stress, which reduced pSTAT3 in the hypothalamus.

Both stress during the prepubertal period and chronic consumption of HFD had long-term sex-specific effects on hormonal signaling related to energy balance. However, the effects of HFD were more pronounced in males, whereas prepubertal stress had greater effects on leptin signaling in females.