To explore a novel adipokine, we screened adipocyte differentiation-related gene and found that TIG2/chemerin was strongly induced during the adipocyte differentiation. Chemerin was secreted by the mature 3T3-L1 adipocytes and expressed abundantly in adipose tissue in vivo as recently described. Intriguingly, the expression of chemerin was differently regulated in the liver and adipose tissue in db/db mice. In addition, serum chemerin concentration was decreased in db/db mice. Chemerin and its receptor/ChemR23 were expressed in mature adipocytes, suggesting its function in autocrine/paracrine fashion. Finally, chemerin potentiated insulin-stimulated glucose uptake concomitant with enhanced insulin signaling in the 3T3-L1 adipocytes. These data establish that chemerin is a novel adipokine that regulates adipocyte function.

Although various function of chemerin have been suggested, its physiological role remains to be elucidated. Here we show that chemerin-deficient mice are glucose intolerant irrespective of exhibiting reduced macrophage accumulation in adipose tissue. The glucose intolerance was mainly due to increased hepatic glucose production and impaired insulin secretion. Chemerin and its receptor ChemR23 were expressed in β-cell. Studies using isolated islets and perfused pancreas revealed impaired glucose-dependent insulin secretion (GSIS) in chemerin-deficient mice. Conversely, chemerin transgenic mice revealed enhanced GSIS and improved glucose tolerance. Expression of MafA, a pivotal transcriptional factor for β-cell function, was downregulated in chemerin-deficient islets and a chemerin-ablated β-cell line and rescue of MafA expression restored GSIS, indicating that chemerin regulates β-cell function via maintaining MafA expression. These results indicate that chemerin regulates β-cell function and plays an important role in glucose homeostasis in a tissue-dependent manner.

A cDNA encoding a rat intestinal Ca 2؉ -independent phospholipase B/lipase (PLB/LIP) was cloned from an ileac mucosa cDNA library using a probe amplified by polymerase chain reaction based on the purified enzyme's sequence. PLB/LIP consists of an NH 2 -terminal signal peptide, four tandem repeats of about 350 amino acids each, and a hydrophobic domain near the COOH terminus. The enzyme purified previously was found to be derived from the second repeat part. To examine the function of each domain, the full-length PLB/LIP, individual repeats, and a protein lacking the COOH-terminal hydrophobic stretch were expressed in COS-7 cells. The results showed that the second repeat, but not the other repeats, had all the activities (phospholipase A 2 , lysophospholipase, and lipase) found in the purified natural and expressed full-length enzymes, suggesting repeat 2 is a catalytic domain. The full-length enzyme was mainly present in membrane fractions and efficiently solubilized by treatment with 1% Triton X-100, but not with phosphatidylinositol-specific phospholipase C. Deletion of the COOH-terminal hydrophobic stretch caused the secretion of >90% of synthesized PLB/LIP into culture media. These results suggest the hydrophobic domain is not replaced by a glycosylphosphatidylinositol anchor but serves as a membrane anchor directly. A message of the full-length PLB/LIP was abundantly expressed in the ileum and also, in a smaller, but significant amount, in the esophagus and testis. Immunohistochemistry showed that PLB/LIP is localized in brush border membranes of the absorptive cells, Paneth cells, and acrosomes of spermatid, suggesting its roles related and unrelated to intestinal digestion.Digestion of phospholipids and triacylglycerol in gastrointestinal tract involves several hydrolysis reactions. A variety of lipases, including acid lipase in lingual gland or stomach, and pancreatic lipase (which is of primary importance in luminal digestion of fats), hydrolyze triacylglycerol to produce monoacylglycerols and free fatty acids (see Refs. 1-3 for reviews)).Pancreatic phospholipases A 2 (PLA 2 ) 1 hydrolyze ester bonds at the sn-2 position of glycerophospholipids and produce fatty acids and lysophospholipids. These steps are prerequisites for lipid absorption by intestinal epithelium cells (4). Lysophospholipid can be directly absorbed, or hydrolyzed by pancreatic lysophospholipase and converted to glycerol 3-phosphate esters and fatty acids.Until recently, all those processes were believed to proceed in the lumen of alimentary tracts by the action of secretory enzymes mentioned above. However, recent studies suggest the presence of a lipid-hydrolyzing enzyme associated with intestinal brush border membranes (5, 6), named phospholipase B/lipase (PLB/LIP) because this enzyme displayed broad lipolytic activities (PLA 2 , lysophospholipase, and lipase activities) (7). PLB/LIP might participate in terminal digestion, or membrane digestion, of dietary lipids and biliary phospholipids, like well established glycosidases and pe...

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