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Adipose tissue metabolism

Obesity has become one of the most pressing health concerns in the United States. With very few (3 as of 2007) drugs approved for long-term treatment, there is a critical need to develop additional therapeutics. Currently available drugs affect metabolism throughout the body and suffer from efficacy limitations and numerous side effects. Accumulating molecular data support an active role for adipose tissue (AT) in the development of obesity and related metabolic diseases. The While a number of AT-derived signaling factors have been identified, the mechanisms by which these factors regulate AT formation remain unclear. In vivo observations in rodents have suggested that enlarged (hypertrophic) fat cells (adipocytes) induce proliferation and recruitment of new adipocytes (hyperplasia) from locally resident precursor cells. In the absence of biochemical details, this phenomenon is still controversial, especially in humans. The goals of this research are: to investigate a hypothesized link between AT metabolism and development; and to engineer an advanced AT model that will support the investigation of cell-cell signaling events in a well-defined, yet physiologically relevant experimental setting. Ultimately, we seek to identify enzyme targets to reduce cellular lipid accumulation and new tissue formation, thereby controlling the excessive expansion of AT in obesity. Our approach involves both experimental and computational efforts to characterize the effects of metabolic modulations on AT signaling and growth.