Hypoadiponectinemia is caused by chronic blockade of nitric oxide synthesis in rats.
Adiponectin is an adipocyte-derived anti-atherogenic protein. Adiponectin levels are decreased in patients and animal models with obesity, diabetes, and coronary artery disease. However, the mechanism by which adiponectin levels are reduced remains unknown. Since hypoadiponectinemia is closely linked to endothelial dysfunction, we examined the regulation of adiponectin in a rat model of chronic blockade of nitric oxide (NO) synthesis by N omega-nitro-L-arginine methyl ester (L-NAME). Decreased production of NO and increased production of O2- were observed in aorta from L-NAME-treated rats. Plasma adiponectin levels and adiponectin mRNA levels of adipose tissue were markedly decreased in L-NAME-treated rats. Cotreatment of pioglitazone (PIO) or allopurinol (ALL) with L-NAME restored plasma adiponectin concentration and fat adiponectin mRNA levels to control levels. Thus, adiponectin levels were decreased in L-NAME-treated rats, however, they returned to normal following administration of PIO due to transcriptional activation of the adiponectin gene, as well as administration of ALL, likely due to elimination of oxidative stress. Oxidative stress appears to be an important cause of hypoadiponectinemia.
Hattori
Sachiko
S
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Hattori
Yoshiyuki
Y
Kasai
Kikuo
K
D052242:Adiponectin; D000273:Adipose Tissue / Q000737:chemistry; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects; D000077205:Pioglitazone; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011921:Rats, Inbred WKY; D013481:Superoxides / Q000378:metabolism; D045162:Thiazolidinediones / Q000494:pharmacology
D052242:Adiponectin; D004791:Enzyme Inhibitors; D007004:Hypoglycemic Agents; D036341:Intercellular Signaling Peptides and Proteins; D012333:RNA, Messenger; D045162:Thiazolidinediones; D013481:Superoxides; D009569:Nitric Oxide; D000493:Allopurinol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D000077205:Pioglitazone