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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.

SUBMITTER: Liu X

PROVIDER: S-EPMC4041709 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Liu Xian X Zhu Zheng Z Kalyani Manu M Janik James M JM Shi Haifei H

Physiology & behavior 20140404

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 int ...[more]

PMID: 24709620

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Project description:BackgroundScientific evidence highlights the influence of biological sex on the relationship between stress and metabolic dysfunctions. However, there is limited understanding of how diet and stress concurrently contribute to metabolic dysregulation in both males and females. Our study aimed to investigate the combined effects of high-fat diet (HFD) induced obesity and repeated stress on fear-related behaviors, metabolic, immune, and hypothalamic outcomes in male and female mice.MethodsTo investigate this, we used a highly reliable rodent behavioral model that faithfully recapitulates key aspects of post-traumatic stress disorder (PTSD)-like fear. We subjected mice to footshock stressor followed by a weekly singular footshock stressor or no stressor for 14 weeks while on either an HFD or chow diet. At weeks 10 and 14 we conducted glucose tolerance and insulin sensitivity measurements. Additionally, we placed the mice in metabolic chambers to perform indirect calorimetric measurements. Finally, we collected brain and peripheral tissues for cellular analysis.ResultsWe observed that HFD-induced obesity disrupted fear memory extinction, increased glucose intolerance, and affected energy expenditure specifically in male mice. Conversely, female mice on HFD exhibited reduced respiratory exchange ratio (RER), and a significant defect in glucose tolerance only when subjected to repeated stress. Furthermore, the combination of repeated stress and HFD led to sex-specific alterations in proinflammatory markers and hematopoietic stem cells across various peripheral metabolic tissues. Single-nuclei RNA sequencing (snRNAseq) analysis of the ventromedial hypothalamus (VMH) revealed microglial activation in female mice on HFD, while male mice on HFD exhibited astrocytic activation under repeated stress.ConclusionsOverall, our findings provide insights into complex interplay between repeated stress, high-fat diet regimen, and their cumulative effects on health, including their potential contribution to the development of PTSD-like stress and metabolic dysfunctions, emphasizing the need for further research to fully understand these interconnected pathways and their implications for health.

Dataset Information

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

Publications

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

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