ADF, novel cytokine PPAR-gamma regulator from fat cells

DESCRIPTION (Scanned from the Applicant's Abstract): Obesity is a major risk factor for diabetes mellitus (type 2; NIDDM). Fat cells secrete both diabetes promoting molecules (fatty acids; TNF-alpha) and at least one molecule 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 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. One of these genes is the nuclear transcription factor PPAR-gamma. This important regulator of adipose cell differentiation is now increasingly recognized as involved in numerous metabolic pathways and neoplasms. PPAR-gamma is activated in vivo and in culture by the thiazolidinedione class of drugs, now widely used as therapeutic agents in diabetes and experimentally in certain human cancers. However, the physiologic regulation of PPAR-gamma itself is not understood. ADF initiates very rapid fat cell differentiation and increases PPAR-gamma mRNA and protein levels. The purification of ADF will permit the development of assays for use in understanding the physiology of ADF and to develop treatments for obesity, diabetes, and other diseases in which PPAR-gamma proves to play a key role. PROPOSED COMMERCIAL APPLICATION: NOT AVAILABLE