The Rui laboratory investigates the physiological and molecular mechanisms of obesity, diabetes, and nonalcoholic fatty liver disease (NAFLD). Body weight is maintained by a balance between energy intake and energy expenditure, and chronic energy imbalance results in obesity. The brain, particularly the hypothalamus, controls energy balance and body weight by sensing and integrating various metabolic signals, including hormones (e.g. leptin and insulin) and nutrients (e.g. glucose and lipids). The ability of the hypothalamus to sense and integrate these signals is regulated by both genetic and environmental factors; impairment in the hypothalamic sensitivity to these signals is a key determinant for energy imbalance and obesity. We study hypothalamic signal transduction pathways (e.g. leptin, insulin, and BDNF signaling pathways) and hypothalamic neural circuits (e.g. the ARC, VMH, DMH, PVN) that regulate energy homeostasis, body weight, and glucose and lipid mobilization and metabolism. We study neuronal and hormonal regulation of adaptive thermogenesis and its role in the development of obesity and diabetes. We investigate hepatocyte-immune cell crosstalk in the liver and the role of inflammatory pathways in NAFLD. Our goal is to identify therapeutic targets for the treatment of obesity, diabetes, and NAFLD.