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Adipose tissue plays a central role in regulating whole-body energy and glucose homeostasis through its subtle functions at both organ and systemic levels. On one hand, adipose tissue stores energy in the form of lipid and controls the lipid mobilization and distribution in the body. On the other hand, adipose tissue acts as an endocrine organ and produces numerous bioactive factors such as adipokines that communicate with other organs and modulate a range of metabolic pathways. Moreover, brown and beige adipose tissue burn lipid by dissipating energy in the form of heat to maintain euthermia, and have been considered as a new way to counteract obesity. Therefore, adipose tissue dysfunction plays a prominent role in the development of obesity and its related disorders such as insulin resistance, cardiovascular disease, diabetes, depression and cancer. In this review, we will summarize the recent findings of adipose tissue in the control of metabolism, focusing on its endocrine and thermogenic function.

Impairments in adiponectin multimerization lead to defects in adiponectin secretion and function and are associated with diabetes, yet the underlying mechanisms remain largely unknown. We have identified an adiponectin-interacting protein, previously named GSTkappa, by yeast 2-hybrid screening. The adiponectin-interacting protein contains 2 thioredoxin domains and has very little sequence similarity to other GST isoforms. However, this protein shares high sequence and secondary structure homology to bacterial disulfidebond A oxidoreductase (DsbA) and is thus renamed DsbA-like protein (DsbA-L). DsbA-L is highly expressed in adipose tissue, and its expression level is negatively correlated with obesity in mice and humans. DsbA-L expression in 3T3-L1 adipocytes is stimulated by the insulin sensitizer rosiglitazone and inhibited by the inflammatory cytokine TNF␣. Overexpression of DsbA-L promoted adiponectin multimerization while suppressing DsbA-L expression by RNAi markedly and selectively reduced adiponectin levels and secretion in 3T3-L1 adipocytes. Our results identify DsbA-L as a key regulator for adiponectin biosynthesis and uncover a potential new target for developing therapeutic drugs for the treatment of insulin resistance and its associated metabolic disorders.obesity ͉ yeast 2-hybrid system ͉ adipose tissue ͉ insulin resistance A diponectin is an adipocyte-derived hormone that plays an important role in the regulation of lipid and glucose metabolism. Adiponectin stimulates fatty acid oxidation, suppresses hepatic gluconeogenesis, increases insulin sensitivity, and acts to counter the effects of the inflammatory cytokine TNF␣. Adiponectin has also been shown to have antiatherogenic effects and to act on the central nervous system to stimulate energy expenditure. Thus, adiponectin is a strong candidate for the development of drugs to treat obesity, insulin resistance, type 2 diabetes, and atherosclerosis (for review, see refs. 1-3).Adiponectin circulating in serum exists primarily in 3 main species: a low-molecular-mass (LMM) trimer of Ϸ67 kDa, a hexamer of Ϸ140 kDa, and a high-molecular-mass (HMM) multimer of Ͼ300 kDa (4-6). The interaction between the collagenous domains results in formation of highly ordered trimer, which is further stabilized by an intratrimer disulfide bond mediated by Cys 39 (or Cys 22 , if the N-terminal 17-aa secretory peptide is excluded). The formation of a disulfide bond between 2 trimers mediated by the free Cys 39 in each leads to the formation of the hexameric form of adiponectin, serving as the building block for the HMM form, which consists of 12-18 hexamers existing in a bouquet-like structure (7). Adiponectin mutants with impaired multimerization are defective in both secretion and function and are associated with diabetes and hypoadiponectinemia (4, 6). More importantly, it has been shown that adiponectin oligomer distribution, rather than its absolute levels, correlates with thiazolidiedionemediated increase in insulin sensitivity (8).A number of studies have shown tha...