New progress in adipocytokine research

Purpose of review The purpose of this review is to discuss newly identified adipocyte-derived signaling molecules—adipocytokines—and to provide our current understanding of the mechanisms through which these factors regulate energy homeostasis. Recent findings Adipose tissue was long known to secrete bioactive substances from fatty acids to steroid hormones. Recent research has disclosed a group of cytokine or cytokine-like molecules such as leptin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), adiponectin, resistin, and PPAR-γ–regulated angiopoietin-related protein (PGAR), among others. These factors play a central role in how the adipocyte communicates with a variety of tissues and allow the adipocyte to sense its own energy stores and to control its own mass. Major recent developments include 1) the identification of AMP-activated protein kinase (AMPK) as a target molecule through which leptin acts in peripheral tissues to induce fat oxidation and reduce lipogenesis, and which mediates leptin's antiosteogenic effect; 2) functional characterization of adiponectin in vivo and in vitro as an insulin sensitizer, in part through activation of AMPK; 3) the understanding that in contrast to prevailing views, the overall effect of IL-6 is protective against obesity, as demonstrated in IL-6 knockout mice; and 4) the insight that PGAR is potentially an important molecule that regulates lipid metabolism. Summary Adipose tissue, as endocrine tissue, secretes a wide range of bioactive substances. Challenges ahead are to define their physiologic roles and to determine to what extent they contribute to pathophysiologic conditions such as obesity, insulin resistance, and type 2 diabetes.