title: Kirenol inhibits adipogenesis through activation of the Wnt/β-catenin signaling pathway in 3T3-L1 adipocytes.
abstract: Kirenol, a natural diterpenoid compound, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities; however, its anti-adipogenic effect remains to be studied. The present study evaluated the effect of kirenol on anti-adipogenesis through the activation of the Wnt/β-catenin signaling pathway. Kirenol prevented intracellular lipid accumulation by down-regulating key adipogenesis transcription factors [peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding proteins α (C/EBPα), and sterol regulatory element binding protein-1c (SREBP-1c)] and lipid biosynthesis-related enzymes [fatty acid synthase (FAS) and acetyl-CoA carboxylase (ACC)], as well as adipocytokines (adiponectin and leptin). Kirenol effectively activated the Wnt/β-catenin signaling pathway, in which kirenol up-regulated the expression of low density lipoprotein receptor related protein 6 (LRP6), disheveled 2 (DVL2), β-catenin, and cyclin D1 (CCND1), while it inactivated glycogen synthase kinase 3β (GSK3β) by increasing its phosphorylation. Kirenol down-regulated the expression levels of PPARγ and C/EBPα, which were up-regulated by siRNA knockdown of β-catenin. Overall, kirenol is capable of inhibiting the differentiation and lipogenesis of 3T3-L1 adipocytes through the activation of the Wnt/β-catenin signaling pathway, suggesting its potential as natural anti-obesity agent.
authors: Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Mi-Bo
authors: MB
authors: Kim
authors: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Youngwoo
authors: Y
authors: Song
authors: Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea.
authors: Changhee
authors: C
authors: Kim
authors: Department of Biomaterials Science and Engineering, Yonsei University, Seoul 120-749, Republic of Korea; Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul 120-749, Republic of Korea. Electronic address: jkhwang@yonsei.ac.kr.
authors: Jae-Kwan
authors: JK
authors: Hwang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D019440:Anti-Obesity Agents / Q000494:pharmacology; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics; D004224:Diterpenes / Q000494:pharmacology*; D015536:Down-Regulation / Q000187:drug effects; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D034622:RNA Interference; D051780:Sterol Regulatory Element Binding Protein 1 / Q000235:genetics; D060449:Wnt Signaling Pathway / Q000187:drug effects*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D019440:Anti-Obesity Agents; D022763:CCAAT-Enhancer-Binding Protein-alpha; D004224:Diterpenes; D047495:PPAR gamma; D051780:Sterol Regulatory Element Binding Protein 1; D051176:beta Catenin; C560087:kirenol
keywords: Adipogenesis; Kirenol; Wnt/β-catenin