Adipocyte Cell Differentiation


Obesity continues to be a global health issue of growing importance due to advances in understanding the negative impact obesity exerts on human health. The increasing percentage of Americans clinically categorized as obese corresponds with health care service reports of high morbidity and mortality from weight-related conditions such as cardiovascular disease, diabetes and certain forms of cancer. The U.S. Surgeon General reports that obesity is responsible for approximately 300,000 deaths annually in the U.S. alone. Understanding the molecular mechanisms underlying obesity has become the object of intense research effort in academic and commercial research enterprises.

Fat cells (adipocytes) typically develop from mesodermal stem cells, which can also differentiate into other mesenchymal cells such as osteoblasts and muscle cells. It has been shown that insulin, insulin-like growth factors, growth hormone, glucocorticoids, and catecholamines affect fat cell proliferation and differentiation in vivo and in vitro. In addition, metalloproteases are also involved in adipogenesis, where they play a significant role in extracellular matrix remodeling (ECM). Adam12 is a member of the family of proteins known as ADAMs, which are a large family of multidomain membrane-anchored proteins that have been implicated in a number of biological activities including myogenesis and adipogenesis. Dr. Harding’s research has shown that, surprisingly, mammalian cells that co-express human HB-EGF and human ADAM-12S stimulate fat production resulting in mature adipocyte production, reducing cellular proliferation and leading to quiescent cells. These results suggest the possibility that such an approach could be used to treat obesity by stimulating the conversion of white fat cells to brown fat cells.

PATENT STATUS: 8,455,191 and 8,835,112

INNVENTORS: Paul Harding and Zhenquing Zhou

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Alicia Knoedler
Vice President for Research & Innovation
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