Adiponectin acts in the brain to decrease body weight.
Adiponectin (ADP) is an adipocyte hormone involved in glucose and lipid metabolism. We detected a rise in ADP in cerebrospinal fluid after intravenous (i.v.) injection, consistent with brain transport. In contrast to leptin, intracerebroventricular (i.c.v.) administration of ADP decreased body weight mainly by stimulating energy expenditure. Full-length ADP, mutant ADP with Cys39 replaced with serine, and globular ADP were effective, whereas the collagenous tail fragment was not. Lep(ob/ob) mice were especially sensitive to i.c.v. and systemic ADP, which resulted in increased thermogenesis, weight loss and reduction in serum glucose and lipid levels. ADP also potentiated the effect of leptin on thermogenesis and lipid levels. While both hormones increased expression of hypothalamic corticotropin-releasing hormone (CRH), ADP had no substantial effect on other neuropeptide targets of leptin. In addition, ADP induced distinct Fos immunoreactivity. Agouti (A(y)/a) mice did not respond to ADP or leptin, indicating the melanocortin pathway may be a common target. These results show that ADP has unique central effects on energy homeostasis.
Qi
Yong
Y
Department of Medicine, Division of Endocrinology, Diabetes and Metabolism, and the Penn Diabetes Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Takahashi
Nobuhiko
N
Hileman
Stanley M
SM
Patel
Hiralben R
HR
Berg
Anders H
AH
Pajvani
Utpal B
UB
Scherer
Philipp E
PE
Ahima
Rexford S
RS
D052242:Adiponectin; D054366:Agouti Signaling Protein; D000818:Animals; D001835:Body Weight / Q000187:drug effects / Q000502:physiology*; D001921:Brain / Q000502:physiology*; D004357:Drug Synergism; D004734:Energy Metabolism / Q000187:drug effects; D007276:Injections, Intraventricular; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D020738:Leptin / Q000008:administration & dosage; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D008820:Mice, Obese; D011506:Proteins / Q000008:administration & dosage / Q000502:physiology*; D011994:Recombinant Proteins / Q000008:administration & dosage
D052242:Adiponectin; D054366:Agouti Signaling Protein; D036341:Intercellular Signaling Peptides and Proteins; D020738:Leptin; D011506:Proteins; D011994:Recombinant Proteins