Effects of energy status and diet on Bdnf expression in the ventromedial hypothalamus of male and female rats

Abstract

Sex differences exist in the regulation of energy homeostasis in response to calorie scarcity or excess. Brain-derived neurotrophic factor (BDNF) is one of the anorexigenic neuropeptides regulating energy homeostasis. Expression of Bdnf mRNA in the ventromedial nucleus of the hypothalamus (VMH) is closely associated with energy and reproductive status. We hypothesized that Bdnf expression in the VMH was differentially regulated by altered energy balance in male and female rats. Using dietary intervention, including fasting-induced negative energy status and high-fat diet (HFD) feeding-induced positive energy status, along with low-fat diet (LFD) feeding and HFD pair-feeding (HFD-PF), effects of diets and changes in energy status on VMH Bdnf expression were compared between male and female rats. Fasted males but not females had lower VMH Bdnf expression than their fed counterparts following 24-hour fasting, suggesting that fasted males reduced Bdnf expression to drive hyperphagia and body weight gain. Male HFD obese and HFD-PF non-obese rats had similarly reduced expression of Bdnf compared with LFD males, indicating that dampened Bdnf expression was associated with feeding a diet high in fat instead of increased adiposity. Decreased BDNF signaling during HFD feeding would increase a drive to eat and may contribute to diet-induced obesity in males. In contrast, VMH Bdnf expression was stably maintained in females when energy homeostasis was disturbed. These results suggest sex-distinct regulation of central Bdnf expression by diet and energy status.

Keywords: Dietary intervention; Estradiol; Glucose; High-fat diet; Leptin.

Fig. 1

Body weight (A–B) and body fat (C–D) of male and female rats before and after 24 h feeding or fasting, and VMH Bdnf expression of male and female rats after 24 h feeding or fasting (E) (Exp 1). *: Different between time points (before and after) within the same dietary treatment. †: Different between dietary groups (feeding and fasting) within the same sex. ‡: Different between sexes (male and female) within the same dietary treatment.

Fig. 2

Daily body weight (A–B), body fat on Day 1 and Day 5 (C–D), and daily caloric intake (E–F) of male and female rats during 4-day LFD or HFD feeding, and VMH Bdnf expression of male and female rats after 4-day LFD or HFD feeding (G) (Exp 2). *: Different compared with day 1 within the same dietary treatment. †: Different between dietary groups (LFD and HFD) within the same sex. ‡: Different between sexes (male and female) within the same dietary treatment.

Fig. 3

Daily body weight (A–B), body fat on Day 1 and Day 28 (C–D), daily caloric intake (E–F), weekly caloric intake (G–H) of male and female rats during 4-week LFD, HFD, or HFD-PF feeding, and VMH Bdnf expression of male and female rats after 4-week LFD, HFD, or HFD-PF feeding (I) (Exp 3). Figs 3A–B, E–F: only significant differences among dietary groups were noted. Figs 3G–H: weeks 1–3 included 7 days and week 4 included 6 days. *: Different compared with day 1 within the same dietary treatment. †: Different among dietary groups (LFD, HFD, and HFD-PF) within the same sex. ‡: Different between sexes (male and female) within the same dietary treatment.

Fig. 3

Daily body weight (A–B), body fat on Day 1 and Day 28 (C–D), daily caloric intake (E–F), weekly caloric intake (G–H) of male and female rats during 4-week LFD, HFD, or HFD-PF feeding, and VMH Bdnf expression of male and female rats after 4-week LFD, HFD, or HFD-PF feeding (I) (Exp 3). Figs 3A–B, E–F: only significant differences among dietary groups were noted. Figs 3G–H: weeks 1–3 included 7 days and week 4 included 6 days. *: Different compared with day 1 within the same dietary treatment. †: Different among dietary groups (LFD, HFD, and HFD-PF) within the same sex. ‡: Different between sexes (male and female) within the same dietary treatment.