Subcutaneous fat in normal and diseased states 3. Adipogenesis: from stem cell to fat cell

The quest for effective strategies to treat obesity has propelled fat research into an exploration of the molecular processes that drive adipocyte formation, and hence body fat mass. The development of obesity is dependent on the coordinated interplay of adipocyte hypertrophy (increased fat cell size), adipocyte hyperplasia (increased fat cell number), and angiogenesis. Evidence suggests that adipocyte hyperplasia, or adipogenesis, occurs throughout life, both in response to normal cell turnover as well as in response to the need for additional fat mass stores that arises when caloric intake exceeds nutritional requirements. Adipogenesis involves two major events-the recruitment and proliferation of adipocyte precursor cells, called preadipocytes, followed by the subsequent conversion of preadipocytes, or differentiation, into mature fat cells. In vitro studies using experimental and primary preadipocyte cell lines have uncovered the mechanisms that drive the adipogenic process, a tightly controlled sequence of events guided by the strict temporal regulation of multiple inhibitory and stimulatory signaling events involving regulators of cell-cycle functions and differentiation factors. This article reviews the current understanding of adipogenesis with emphasis on the various stages of adipocyte development; on key hormonal, nutritional, paracrine, and neuronal control signals; as well as on the components involved in cell-cell or cell-matrix interactions that are pivotal in regulating fat cell formation. Special consideration is given to clinical applications derived from adipogenesis research with impact on medical, surgical and cosmetic fields.