title: AICAR, an activator of AMPK, inhibits adipogenesis via the WNT/β-catenin pathway in 3T3-L1 adipocytes.
abstract: AMP-activated protein kinase (AMPK) is known to sense the cellular energy state and regulates various cellular energy metabolism pathways through its activation by AMP, an indicator of a low-energy state. 5-Aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR), an activator of AMPK, efficiently inhibited the adipogenesis of 3T3-L1 cells. To elucidate its possible mechanism of action, the expression levels of β-catenin and other members of the WNT/β-catenin pathway were analyzed during the adipogenesis of 3T3-L1 cells in the presence or absence of AICAR. It was found that AICAR significantly enhanced β-catenin expression and its nuclear accumulation. Transfection of β-catenin small interfering RNA (siRNA) significantly prevented the effects of AICAR on the expression of various genes. The expression of the major genes of adipogenesis including the peroxisome proliferator-activated receptor (PPAR)γ, the CCAAT/enhancer binding protein (C/EPB)α, the fatty acid binding protein (FABP)4 and lipoprotein lipase (LPL), which were all reduced by AICAR treatment, were significantly recovered in β-catenin siRNA-transfected cells. Among the members of the WNT/β-catenin pathway, the expression of low density lipoprotein receptor-related protein (LRP)6, dishevelled (DVL)2 and DVL3 were significantly up-regulated by AICAR treatment, whereas the expression of AXIN was down-regulated. The present study provides compelling evidence that AICAR inhibits adipogenesis through the modulation of the WNT/β-catenin pathway.
authors.affiliation: Department of Microbiology, Chung-Ang University College of Medicine, Dongjak-gu, Seoul 156-756, Republic of Korea.
authors.forename: Haeyong
authors.initials: H
authors.lastname: Lee
authors.forename: Ryunhwa
authors.initials: R
authors.lastname: Kang
authors.forename: Sungmin
authors.initials: S
authors.lastname: Bae
authors.forename: Yoosik
authors.initials: Y
authors.lastname: Yoon
mesh_terms: D041721:3T3-L1 Cells; D000091162:AMP-Activated Protein Kinase Kinases; D017667:Adipocytes / Q000187:drug effects*; D050156:Adipogenesis / Q000187:drug effects*; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D051379:Mice; D011494:Protein Kinases / Q000378:metabolism*; D034741:RNA, Small Interfering; D012265:Ribonucleotides / Q000494:pharmacology*; D051153:Wnt Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: D034741:RNA, Small Interfering; D012265:Ribonucleotides; D051153:Wnt Proteins; D051176:beta Catenin; D000620:Aminoimidazole Carboxamide; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; C031143:AICA ribonucleotide