AICAR, an activator of AMPK, inhibits adipogenesis via the WNT/β-catenin pathway in 3T3-L1 adipocytes

• Published in: International journal of molecular medicine Vol. 28; no. 1; pp. 65 - 71
• Main Authors: Lee, Haeyong, Kang, Ryunhwa, Bae, Sungmin, Yoon, Yoosik
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01.07.2011
• Subjects: 3T3-L1 Cells; Adipocytes - drug effects; Adipogenesis - drug effects; Aminoimidazole Carboxamide - analogs & derivatives; Aminoimidazole Carboxamide - pharmacology; Animals; beta Catenin - genetics; beta Catenin - metabolism; Gene Expression Profiling; Gene Regulatory Networks; Mice; Protein Kinases - metabolism; Ribonucleotides - pharmacology; RNA, Small Interfering; Wnt Proteins - genetics; Wnt Proteins - metabolism
• ISSN: 1107-3756; 1791-244X
• DOI: 10.3892/ijmm.2011.674

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.