Adiponectin stimulates AMP-activated protein kinase in the hypothalamus and increases food intake.
Adiponectin has been shown to stimulate fatty acid oxidation and enhance insulin sensitivity through the activation of AMP-activated protein kinase (AMPK) in the peripheral tissues. The effects of adiponectin in the central nervous system, however, are still poorly understood. Here, we show that adiponectin enhances AMPK activity in the arcuate hypothalamus (ARH) via its receptor AdipoR1 to stimulate food intake; this stimulation of food intake by adiponectin was attenuated by dominant-negative AMPK expression in the ARH. Moreover, adiponectin also decreased energy expenditure. Adiponectin-deficient mice showed decreased AMPK phosphorylation in the ARH, decreased food intake, and increased energy expenditure, exhibiting resistance to high-fat-diet-induced obesity. Serum and cerebrospinal fluid levels of adiponectin and expression of AdipoR1 in the ARH were increased during fasting and decreased after refeeding. We conclude that adiponectin stimulates food intake and decreases energy expenditure during fasting through its effects in the central nervous system.
Kubota
Naoto
N
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Yano
Wataru
W
Kubota
Tetsuya
T
Yamauchi
Toshimasa
T
Itoh
Shinsuke
S
Kumagai
Hiroki
H
Kozono
Hideki
H
Takamoto
Iseki
I
Okamoto
Shiki
S
Shiuchi
Tetsuya
T
Suzuki
Ryo
R
Satoh
Hidemi
H
Tsuchida
Atsushi
A
Moroi
Masao
M
Sugi
Kaoru
K
Noda
Tetsuo
T
Ebinuma
Hiroyuki
H
Ueta
Yoichi
Y
Kondo
Tatsuya
T
Araki
Eiichi
E
Ezaki
Osamu
O
Nagai
Ryozo
R
Tobe
Kazuyuki
K
Terauchi
Yasuo
Y
Ueki
Kohjiro
K
Minokoshi
Yasuhiko
Y
Kadowaki
Takashi
T
D055372:AMP-Activated Protein Kinases; D000256:Adenoviridae / Q000235:genetics; D052242:Adiponectin / Q000134:cerebrospinal fluid / Q000235:genetics / Q000502:physiology*; D052436:Adipose Tissue, White / Q000166:cytology / Q000378:metabolism; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism; D004435:Eating; D004734:Energy Metabolism; D005260:Female; D007031:Hypothalamus / Q000201:enzymology* / Q000473:pathology; D007124:Immunoenzyme Techniques; D017403:In Situ Hybridization; D020738:Leptin / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009097:Multienzyme Complexes / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D015347:RNA Probes; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D054411:Receptors, Leptin
D052242:Adiponectin; D020738:Leptin; D009097:Multienzyme Complexes; D015347:RNA Probes; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D054411:Receptors, Leptin; C475419:adiponectin receptor 1, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases