With obesity reaching epidemic proportions, the medical consequences of comorbidities such as diabetes, cardiovascular disease, and neuropsychiatric disorders, among others, require novel therapeutic approaches. Our research focuses on the neural control of metabolism, including energy balance, glucose, and lipoprotein metabolism. We have utilized rodent models to understand signal transduction mechanisms by which peripheral hormones regulate neuroendocrine function. These studies have been extended into high-fat feeding models of obesity where acquired resistance to hormonal modulators of feeding occurs. High-fat feeding leads to central nervous system inflammation, and targeting inflammatory pathways normalizes feeding. Interestingly, high fat also contributes to behaviors in rodents that resemble human neuropsychiatric disorders, and we are increasingly interested in understanding shared neurobiological mechanisms involved in obesity and comorbid neuropsychiatric disorders.
Interventional interests include understanding how dietary macronutrient composition modulates CNS dysfunction and risk for metabolic syndrome. For example, while the saturated fatty acid palmitate potently induces mitochondrial dysfunction, reactive oxygen species production, and inflammation, the monounsaturated fatty acid oleate largely protects against these effects in cells, animals, and human subjects. We additionally seek to develop macronutrient approaches to weight loss and modulation of body composition and to increase our understanding of central nervous system changes in humans with obesity and diabetes.