title: Dioscin inhibits adipogenesis through the AMPK/MAPK pathway in 3T3-L1 cells and modulates fat accumulation in obese mice.
abstract: Dioscin (DS) is a steroidal saponin present in a number of medicinal plants and has been shown to exert anticancer, antifungal and antiviral effects. The present study aimed to deternube the effects DS on the regulation of adipogenesis and to elucidate the underlying mechanisms. In vitro experiments were performed using differentiating 3T3-L1 cells treated with various concentrations (0-4 µM) of DS for 6 days. A cell viability assay was performed on differentiating cells following exposure to DS. Oil Red O staining and triglyceride content assay were performed to evaluate the lipid accumulation in the cells. We also carried out the following experiments: i) flow cytometry for cell cycle analysis, ii) quantitative reverse transcription polymerase chain reaction for measuring adipogenesis-related gene expression, and iii) western blot analysis to measure the expression of adipogenesis transcription factors and AMP-activated protein kinase (AMPK), acetyl-CoA carboxylase (ACC) and mitogen-activated protein kinase (MAPK) phosphorylation. In vivo experiements were performed using mice with obesity induced by a high-fat diet (HFD) that were treated with or without DS for 7 weeks. DS suppressed lipid accumulation in the 3T3-L1 cells without affecting viability at a dose of up to 4 µM. It also delayed cell cycle progression 48 h after the initiation of adipogenesis. DS inhibited adipocyte differentiation by the downregulation of adipogenic transcription factors and attenuated the expression of adipogenesis-associated genes. In addition, it enhanced the phosphorylation of AMPK and its target molecule, ACC, during the differentiation of the cells. Moreover, the inhibition of adipogenesis by DS was mediated through the suppression of the phosphorylation of MAPKs, such as extracellular-regulated kinase 1/2 (ERK1/2) and p38, but not c-Jun-N-terminal kinase (JNK). DS significantly reduced weight gain in the mice with HFD-induced obesity; this was evident by the suppression of fat accumulation in the abdomen. the present study reveals an anti-adipogenic effect of DS in vitro and in vivo and highlights AMPK/MAPK signaling as targets for DS during adipogenesis.
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Barun
authors.initials: B
authors.lastname: Poudel
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Seong-Won
authors.initials: SW
authors.lastname: Lim
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Hyeon-Hui
authors.initials: HH
authors.lastname: Ki
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Sarmila
authors.initials: S
authors.lastname: Nepali
authors.affiliation: Department of Oriental Pharmacy, College of Pharmacy and Wonkwang-Oriental Medicines Research Institute, Wonkwang University, Iksan, Jeonbuk 570-749, Republic of Korea.
authors.forename: Young-Mi
authors.initials: YM
authors.lastname: Lee
authors.affiliation: Department of Immunology and Institute of Medical Sciences, Chonbuk National University Medical School, Jeonju, Jeonbuk 561-756, Republic of Korea.
authors.forename: Dae-Ki
authors.initials: DK
authors.lastname: Kim
mesh_terms: D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D000103:Acetyl-CoA Carboxylase / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D001823:Body Composition / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D059305:Diet, High-Fat / Q000009:adverse effects; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000494:pharmacology; D015536:Down-Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014280:Triglycerides / Q000378:metabolism; D015430:Weight Gain / Q000187:drug effects*
chemical_list: D014280:Triglycerides; C019357:dioscin; D020928:Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D004144:Diosgenin