Leptin Signaling and Sex Differences in Vagal Pathways Regulates Energy Balance
- ISBN-10
- ISBN-13
- 9798691213182
- Language
- English
- Published
- 2020
- Author
- Kuei-Pin Huang
Description
The vagal pathway serves as a conduit linking visceral organs and the central nervous system (CNS), and this pathway is essential in regulation of food intake and coordination of the digestive system in the postprandial phase. Short-term consumption of a high-fat diet (HF) impairs the sensitivity of vagal afferents by inducing resistance to leptin, a hormone regulating long-term energy balance. Reduced responsiveness to gastrointestinal signals in vagal afferent neurons (VAN) results in increased food intake and body weight; however, the effect of vagal leptin resistance on the digestive system is unknown. Estradiol, an ovarian hormone, modulates energy balance by suppression of food intake and increased energy expenditure. A resistance to HF-induced obesity in female animal models and lower prevalence of overweight in women suggest that estradiol has a protective effect against diet-induced energy imbalance. However, the sex differences in the early stage of obesity development and food intake regulation at the level of vagal pathway remains unclear. The first part of dissertation shows the sex difference in systemic energy balance after short-term HF feeding. Female mice are less vulnerable to diet-induced weight gain due to higher energy expenditure and the prevention of development of hyperphagia. The second part of the dissertation demonstrates the importance of vagal leptin signaling in different physiological functions, including ovarian function and digestive system. Lack of leptin signaling in VAN disrupts ovarian production of estradiol, which in turn increases food intake associated with more frequent meals. This is likely due to increased vagus-mediated orexigenic action of ghrelin. In addition to reducing ovarian function, impairment of vagal leptin signaling leads to malabsorption of luminal carbohydrates from HF. Decreased absorption of intestinal glucose is followed by the downregulation of long-term energy storage in liver and adipose tissue. Overall, these findings fill the gap in our knowledge of sex difference in the pathogenesis of diet-induced obesity and the importance of leptin signaling in VAN to support ovarian function and the digestive system. A better understanding of vagus-mediated food intake regulation might benefit the development of periphery-based medication for obesity.
