Neural and hormonal control of food intake and body weight; communication between gut and brain; obesity, diabetes and related metabolic disorders; physiological and behavioral responses to overfeeding, palatable foods, dieting and starvation.
Current Research
What causes the feelings of hunger and fullness? What makes you decide to stop eating at the end of a meal? Why do some people seem naturally thin while others are prone to weight gain and obesity? My laboratory uses rodent models to investigate the diverse factors that control food intake and body weight. An important class of hormones contributing to energy balance are "adiposity signals," which inform the brain of how much body fat an individual carries. Perhaps the most well studied adiposity signal is leptin, which is secreted by fat cells in proportion to body fat mass. Leptin levels change when body fat mass changes, during fasting or weight gain, for example. Another class of signals that contribute to food intake control are shorter-term in nature, arising from the gastrointestinal tract in response to ingested nutrients. These "satiety signals" alert the brain to the presence of incoming food, and contribute to an individual's feeling of fullness at the end of a meal. Adiposity and satiety signals interact synergistically. That is, when leptin levels are high, animals respond more strongly to satiety signals. Conversely, when leptin levels are low or leptin signaling is reduced, animals' ability to respond to satiety signals is impaired.
Some of our specific questions include:
Which neural circuits mediate the interactions between these different adiposity and satiety signals?
What role do these interactions play in the control of food intake under healthy conditions and in pathological states?
What role might these interactions play in the response to different diets (e.g, high-fat, highly palatable foods)?
To address these questions, we employ normal and genetically modified animal models and a variety of techniques including pharmacology, neuroanatomy and histochemistry, surgical manipulation of the gut and brain, measurement of circulating hormones and fuels, and detailed behavioral analysis.
Publications
Selected Publications
Williams DL. Finding the sweet spot: Peripheral vs. central GLP-1 in feeding and glucose homeostasis. Endocrinology, In Press, 2009
Williams DL, Baskin DG, Schwartz MW. Evidence that intestinal GLP-1 plays a physiological role in satiety. Endocrinology. In Press, 2009
Williams DL, Schwartz MW, Bastian LS, Blevins JE, Baskin DG. Immunocytochemistry and Laser Capture Microdissection for Real-time Quantitative PCR Identify Hindbrain Neurons Activated by Interaction Between Leptin and Cholecystokinin. J Histochem Cytochem, 56(3):285-93, 2008.
Williams DL, Baskin DG, Schwartz MW. Leptin regulation of the anorexic response to glucagon like peptide-1 receptor stimulation. Diabetes, 55(12): 3387-3393, 2006.
Williams DL and Schwartz MW. The melanocortin system as a central integrator of direct and indirect controls of food intake. Am J Physiol Regul Integr Comp Physiol 289(1): R2-3, 2005.
