Sex steroids regulate body weight and energy homeostasis, but central mechanisms underlying these effects are not fully elucidated. This research proposal aims to establish the medial amygdala (MeA) as an integrating center for neurosteroid testosterone/estrogen signaling in energy homeostasis. Results from this work will provide some important clues regarding one of the fundamental mechanisms contributing to body weight control.
The gut microbiota has recently been identified to contribute to obesity, insulin resistance, and the subsequent development of T2D, but how it modulates metabolism is unclear. We propose to determine if gut microbiota-derived nutrient metabolites, short chain fatty acids (SCFAs), act on the central nervous system (CNS) to regulate body weight balance. Moreover, we will assess if dysfunction of this central pathway contributes to the development of obesity, and ultimately if enhancement of its functions can treat obesity and prevent diabetes.
The ovarian hormone, estrogen, regulates both body temperature and body weight, but central mechanisms for estrogen-mediated modulation on metabolic adaptation during temperature or nutritional challenges are still unknown. The project aims to define and understand the neural basis of estrogenic regulation of metabolic adaptation in response to temperature change in both females and males.
It is well accepted that circulating leptin secreted from white adipose tissue functions as a negative feedback signal to the brain to regulate energy homeostasis. However, the metabolic role of leptin produced from interscapular brown adipose tissue (IBAT) is still unknown. We aim to unravel the molecular and neurocircuitry mechanisms for a leptin-initiated interoceptive network between IBAT and the brain and test if this connection contributes to the regulation of fast-induced food intake and systemic energy homeostasis.
