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 micro g/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.