Nitric oxide (NO) stimulates mitochondrial biogenesis. We recently reported that adiponectin synthesis is regulated by mitochondrial function in adipocytes. This study was undertaken to test the hypothesis that endothelial NO synthase (eNOS) plays an important role in adiponectin synthesis by producing NO and enhancing mitochondrial function in adipocytes. We examined the effects of eNOS knockdown on adiponectin synthesis in 3T3-L1 adipocytes and also examined plasma adiponectin levels and the mitochondria in adipose tissue of eNOS knockout (eNOS Ϫ/Ϫ ) mice with and without chronic administration of a NO donor. In cultured 3T3-L1 adipocytes, eNOS siRNA decreased rosiglitazone-induced adiponectin secretion, which was associated with decreases in mitochondrial proteins and biogenesis factors. Plasma adiponectin concentrations were reduced in adult eNOS Ϫ/Ϫ mice compared with age-matched wild-type mice. Mitochondrial contents in adipose tissue were reduced in eNOS Ϫ/Ϫ mice, and this was associated with decreased expression of mitochondrial biogenesis factors, increased levels of 8-hydroxyguanosine, a biomarker of oxidative stress, and morphological abnormalities in mitochondria. Rosiglitazone-induced increases in adiponectin expression and mitochondrial content were also reduced significantly in eNOS Ϫ/Ϫ mice. Chronic administration of a NO donor reversed mitochondrial abnormalities and increased adiponectin expression in adipose tissue of eNOS Ϫ/Ϫ mice. eNOS plays an important role in adiponectin synthesis in adipocytes by increasing mitochondrial biogenesis and enhancing mitochondrial function. endothelial nitric oxide synthase; mitochondrial biogenesis; oxidative stress; nitric oxide ADIPONECTIN, ONE OF THE ADIPOCYTE HORMONES, has many favorable effects on metabolism, including improvement of insulin action and reduction of atherosclerotic processes and cancer (1,13,17,18,36). Unlike other adipocytokines, the plasma level of adiponectin is reduced in obese individuals due to selective suppression of its synthesis in adipocytes. We recently reported that mitochondrial function is essential for adiponectin synthesis in adipocytes, and mitochondrial dysfunction in adipose tissue explains decreased adiponectin synthesis in obesity (16). This study demonstrated that plasma adiponectin levels and adiponectin expression in adipose tissue were profoundly reduced in obese db/db mice, which was associated with decreased adipose tissue mitochondrial content and function. In addition, rosiglitazone, a peroxisome proliferator-activated receptor-␥ (PPAR␥) agonist, normalized plasma adiponectin levels and adiponectin expression in obese db/db mice by reversing the changes in mitochondrial content and function in adipose tissue.Nitric oxide (NO) has been shown to stimulate mitochondrial biogenesis (30, 31), and evidence has accumulated that NO synthases play a crucial role in energy metabolism (14,24). Among the known NO synthases, endothelial NO synthase (eNOS) was identified originally as playing an important role in the regu...

-Abstract --Abstract --Abstract --AbstractClusterin is a highly glycosylated heterodimeric glycoprotein that plays diverse biological roles in various organs. The secreted clusterin has been established as a major form of the protein that exerts diverse tissue effects. For instance, clusterin is known to act in cell protection through the actions of extra-cellular molecular chaperones. In the extracellular milieu, clusterin participates in specific interactions with a diverse array of native biological molecules including LRP-2 (Lipoprotein receptor-related protein 2, also known as gp330 or megalin), which is involved in ligand endocytosis at the surfaces of certain epithelia. Clusterin is expressed transiently in developing and differentiating endocrine pancreatic cells and might be involved in pancreas development. This transient expression of clusterin at specific time points of pancreas development and cell differentiation during pancreas regeneration implies that the protein is a regulatory factor for cytodifferentiation as well as for replication. A specific action of the clusterin in the reconstruction and remodeling of the endocrine pancreas has been demonstrated. It also strongly stimulates duct cell differentiation into insulin-secreting cells under in vitro culture conditions. Clusterin appears thus as a potent regulator of insulin cell morphogenesis. (J Kor Diabetes