We are investigating the physiology of energy homeostasis and its role in obesity and diabetes. We integrate molecular biology with physiology, chiefly using the mouse as a model system. One research focus is on leptin, a hormone made in adipose cells that is important for adaptation to starvation and in feedback regulation of energy expenditure and adiposity. We are characterizing the transcription factors controlling leptin expression and how the cell type, level of adipose stores, and hormonal milieu regulate leptin transcription. Since energy expenditure is crucial to the defense against obesity, energy expenditure is also an interest. We discovered a gene, uncoupling protein-3 (ucp3) that is expressed in muscle and adipose tissue. Ucp3 is homologous to ucp1, which is responsible for 'wasting' energy as heat. Ucp3 is regulated by thyroid hormone, beta3-adrenergic agonist, and fasting and thus may mediate some of the changes in energy expenditure caused by these agents/conditions. A third line of investigation is a transgenic mouse lacking white fat. This mouse is a good model of humans with lipoatrophic diabetes. We are studying these mice to try to understand how the lack of fat causes diabetes, which is an intriguing contrast to the more common situation in which excess fat causes diabetes.
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