Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow (Ay/a) Obese Mice

Peripheral, But Not Central, Administration of Adiponectin Reduces Visceral Adiposity and Upregulates the Expression of Uncoupling Protein in Agouti Yellow ( A y /a ) Obese Mice Takayuki Masaki 1 , Seiichi Chiba 1 , Tohru Yasuda 1 , Tetsuo Tsubone 1 , Tetsuya Kakuma 1 , Iichiro Shimomura 2 , Tohru Funahashi 3 , Yuji Matsuzawa 3 and Hironobu Yoshimatsu 1 1 Department of Internal Medicine, School of Medicine, Oita Medical University, Oita, Japan 2 Department of Medicine and Pathophysiology, Graduate School of Medicine, Osaka University, Osaka, Japan 3 Department of Internal Medicine, Graduate School of Medicine, Osaka University, Osaka, Japan Address correspondence and reprint requests to Dr. Takayuki Masaki, Department of Internal Medicine, School of Medicine, Oita Medical University, Hasama, Oita, 879-5593, Japan. E-mail: masaki{at}oita-med.ac.jp Abstract To examine the peripheral and central roles of adiponectin in energy intake and expenditure, we investigated the effects of adiponectin on food intake, adiposity, sympathetic nerve activity (SNA), and mRNA expressions of uncoupling protein (UCP) in the brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle in agouti yellow ( A y /a ) obese mice. Intraperitoneal administration of adiponectin (1.5 mg/kg for 7 days) attenuated body weight gain and reduced visceral adiposity in A y /a obese mice compared with PBS-treated controls. In addition, adiponectin treatment increased the expression of UCP1 mRNA in BAT, UCP2 mRNA in WAT, and UCP3 mRNA in skeletal muscle compared with PBS-treated A y /a controls. Acute peripheral administration of adiponectin (1.5 mg/kg, one injection) also increased SNA in the BAT accompanied by an increase in rectal temperature. Finally, these above responses as well as expression of c-Fos–like immunohistochemistry in the hypothalamus were not induced by central application of adiponectin (0–15 μg/kg). Taken together, adiponectin effectively regulated visceral adiposity, SNA, and UCP mRNA expression peripherally, suggesting that this substance can be used as a therapeutic tool, administered peripherally, in the treatment of visceral obesity and related metabolic disorders. ARC, arcuate nucleus BAT, brown adipose tissue ICV, intracerebroventricular PVN, paraventricular nucleus SNA, sympathetic nerve activity UCP, uncoupling protein VMH, ventromedial hypothalamus WAT, white adipose tissue Footnotes Accepted June 18, 2003. Received March 18, 2003. DIABETES