My research mainly focuses on age-related and diet-induced obesity from the perspectives of leptin function and resistance and the association between leptin resistance and obesity. The ultimate goal of this line of research is to gain mechanistic insights from rodent studies, to understand how humans gain weight with age and diets, and to develop new strategies to both produce weight loss and to maintain the weight reduction in the long run. The major means of intervention for alleviating obesity are chronic gene therapy combined with traditional pharmacological drug administration. Recent investigations involve the brain’s melanocortin pathway that mediates leptin’s action in the central nervous system and affects the long-term regulation of energy balance. In addition, we are also examining leptin function specifically in the midbrain reward center, the ventral tegmental area (VTA), to curb high-fat consumption, alter dietary preference and deter diet-induced obesity. Rodents exhibiting obesity-prone and dietary resistance characteristics are employed to elucidate a potential mechanistic link between deficient leptin signaling/function in the VTA and heightened preference for palatable fattening foods and the vulnerability to dietary obesity.