ADF--A NOVEL CYTOKINE INVOLVED IN ADIPOGENESIS

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Obesity is a major risk factor for diabetes mellitus (type 2; NIDDM), but how the fat cell mass disturbs metabolism and produces the insulin resistance, hyperglycemia, hyperlipidemia, and hypertension that are the hallmarks of diabetes is unknown. Fat cells secrete both diabetes promoting molecules (fatty acids; TNF-alpha) and at least one that may be antidiabetic (leptin). We have partially purified a new protein (cytokine) which is also secreted by mature adipocytes, adipocyte differentiation factor (ADF). We hypothesize that ADF may also have antidiabetic action, since, like the antidiabetic thiazolidinedione drugs, it induces fat cell differentiation and is a positive regulator for genes involved in the control of adipose cell proliferation and glucose metabolism. In order to study the role of ADF in obesity and diabetes, we will using 3T3-L1 adipocyte conditioned medium to first purify the ADF protein to homogeneity. After obtaining partial amino acid sequences; we will make antibodies, clone its cDNA, and produce recombinant ADF protein. These studies will provide a basic understanding of adipocyte cell conversion and make available a protein that can lead to the development of important reagents for use in the development of diagnostic tests and treatments of obesity, diabetes and their associated diseases. PROPOSED COMMERCIAL APPLICATIONS: Since ADF causes differentiation of preadipocyte cells, this project will lead to development of important reagents to study adipogenesis and novel therapeutics with applications in adipose tissue formation and tissue engineering.