This application claims benefit as a divisional of U.S. patent application Ser. No. 10/785,720, filed Feb. 24, 2004, which in turn claims benefit of U.S. provisional patent application No. 60/449,489, filed Feb. 24, 2003, both of which are hereby incorporated by reference in their entireties.
This invention was made with government support under NIH Grant Number DK57835, awarded by the National Institutes of Health. The U.S. government has certain rights in this invention.
The present invention relates to isolated polypeptides that selectively express in fat tissue, as well as methods for use of the polypeptides.
Obesity affects a growing number of the U.S. population and often is closely associated with insulin resistance, type 2 diabetes, cardiovascular disease, and dyslipidemia. Obesity itself is typically a heterogeneous condition, due to regional distribution of fat tissue. Central obesity generally refers to fat accumulation in omental or visceral cavity, whereas peripheral obesity generally refers the subcutaneous fat accumulation. Epidemiological studies have established that central obesity is associated with a higher degree of risk than peripheral obesity to the above-mentioned diseases, however, the underlying mechanism(s) are generally not well understood. Presumably, distinctive biological properties of omental fat, in addition to its unique anatomical location, contribute to the increased pathogenecity of central obesity. It has been discovered that an excess of cortisol can cause central obesity and that treatment of HIV patients with protease inhibitor can lead to accumulation of omental fat accumulation but depletion of subcutaneous fat. In vitro studies have also demonstrated that abdominal visceral fat pads can be relatively resistant to the anti-lipolytic effect of insulin and susceptible to the lipolytic effect of catecholamine. At a molecular level, omental fat has been shown to have increased gene expression or secretion of interleukin 6, plasminogen activator inhibitor (PAI-1), and angiotensinogen, compared to subcutaneous fat. These observations indicate the existence of biological difference between omental and subcutaneous fat depots.
Adipose, i.e., fat, tissue plays a critical role in the pathogenesis of obesity and its associated diseases, but the molecular mechanisms for these associations generally remain unclear. Adipose tissue is generally recognized as an important endocrine organ that communicates actively with the central nervous system and other peripheral tissues through the release of a variety of bioactive factors that regulate glucose and lipid homeostasis. These factors, collectively known as adipocytokines, include leptin, tumor-necrosis factor α (TNFα), plasminogen activator inhibitor-1 (PAI-1), adiponectin/ACRP30/adipoQ, and resistin. Adipocytokines have been demonstrated to play a key role in the pathogenesis of obesity and its associated diseases. Nevertheless, current knowledge of known genes generally cannot fully explain the pathophysiology of obesity, and effective treatment for these diseases is still lacking.
