Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway.
Adiponectin, one of the insulin-sensitizing adipokines, has been shown to activate fatty acid oxidation in liver and skeletal muscle, thus maintaining insulin sensitivity. However, the precise roles of adiponectin in fatty acid synthesis are poorly understood. Here we show that adiponectin administration acutely suppresses expression of sterol regulatory element-binding protein (SREBP) 1c, the master regulator which controls and upregulates the enzymes involved in fatty acid synthesis, in the liver of +Lepr(db)/+Lepr(db) (db/db) mouse as well as in cultured hepatocytes. We also show that adiponectin suppresses SREBP1c by AdipoR1, one of the functional receptors for adiponetin, and furthermore that suppressing either AMP-activated protein kinase (AMPK) via its upstream kinase LKB1 deletion cancels the negative effect of adiponectin on SREBP1c expression. These data show that adiponectin suppresses SREBP1c through the AdipoR1/LKB1/AMPK pathway, and suggest a possible role for adiponectin in the regulation of hepatic fatty acid synthesis.
Awazawa
Motoharu
M
Department of Metabolic Diseases, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Ueki
Kohjiro
K
Inabe
Kazunori
K
Yamauchi
Toshimasa
T
Kaneko
Kazuma
K
Okazaki
Yukiko
Y
Bardeesy
Nabeel
N
Ohnishi
Shin
S
Nagai
Ryozo
R
Kadowaki
Takashi
T
D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D052242:Adiponectin / Q000235:genetics / Q000494:pharmacology / Q000502:physiology; D000818:Animals; D005227:Fatty Acids / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D011494:Protein Kinases / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D054419:Receptors, Adiponectin / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D051780:Sterol Regulatory Element Binding Protein 1 / Q000096:biosynthesis*
D052242:Adiponectin; C499919:Adipoq protein, mouse; D005227:Fatty Acids; D054419:Receptors, Adiponectin; D011994:Recombinant Proteins; C497388:Srebf1 protein, mouse; D051780:Sterol Regulatory Element Binding Protein 1; C475419:adiponectin receptor 1, mouse; D011494:Protein Kinases; D017346:Protein Serine-Threonine Kinases; C491654:Stk11 protein, mouse; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases