title: Cascade regulation of PPARγ(2) and C/EBPα signaling pathways by celastrol impairs adipocyte differentiation and stimulates lipolysis in 3T3-L1 adipocytes.
abstract: OBJECTIVE
  Celastrol, a triterpene from the root bark of the Chinese medicinal plant Tripterygium wilfordii, has been shown to exhibit anti-oxidant, anti-inflammatory, anti-cancer and insecticidal activities. Also, it has been demonstrated that celastrol has obesity-controlling effects in diet-induced obesity mice. However, direct evidence that celastrol contributes to the development of adipocyte differentiation and lipolysis has not been fully elucidated. Moreover, no previous studies have evaluated whether celastrol may regulate adipogenic transcriptional markers in adipocytes.
  
  
  METHODS
  In order to address the questions above, we extended previous observations and investigated in vitro celastrol signaling study whether celastrol may regulate differentiation, lipolysis and key adipogenic transcriptional pathways in 3T3-L1 adipocytes.
  
  
  RESULTS
  Treatment of celastrol not only inhibited adipocyte differentiation (lipid accumulation, glyceraldehyde-3-phosphate dehydrogenase activity and triglyceride content) but also increased lipolysis (glycerol release and free fatty acid release) in 3T3-L1 adipocytes. In addition, all celastrol-regulated functional activities were controlled by PPARγ(2) and C/EBPα signaling pathways in duration of celastrol's treatment in 3T3-L1 adipocytes.
  
  
  CONCLUSIONS
  Our initial data from in vitro celastrol signaling studies suggest novel insights into the role of PPARγ(2) and C/EBPα as probable mediators of the action of celastrol in regulating adipocyte differentiation and lipolysis in 3T3-L1 adipocytes.
authors.affiliation: Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, South Korea.
authors.forename: Seung Kug
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, South Korea.
authors.forename: Sunmi
authors.initials: S
authors.lastname: Park
authors.affiliation: Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, South Korea.
authors.forename: Subin
authors.initials: S
authors.lastname: Jang
authors.affiliation: Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, South Korea.
authors.forename: Hun Hee
authors.initials: HH
authors.lastname: Cho
authors.affiliation: Mibyeong Research Center, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea.
authors.forename: Siwoo
authors.initials: S
authors.lastname: Lee
authors.affiliation: Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, South Korea; Cell Function Regulation Laboratory, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea.
authors.forename: Seungkwon
authors.initials: S
authors.lastname: You
authors.affiliation: Mibyeong Research Center, Korea Institute of Oriental Medicine, Daejeon 34054, South Korea. Electronic address: kataz@kiom.re.kr.
authors.forename: Sang-Hyuk
authors.initials: SH
authors.lastname: Kim
authors.affiliation: Laboratory of Metabolic Engineering, Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02841, South Korea; Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, South Korea; Biomedical Research Center of Guro Hospital, Research Driven Hospital, Korea University, Seoul 08308, South Korea. Electronic address: mhs72@korea.ac.kr.
authors.forename: Hyun-Seuk
authors.initials: HS
authors.lastname: Moon
mesh_terms: D041721:3T3-L1 Cells; D052438:Adipocytes, White / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects / Q000494:pharmacology; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000009:adverse effects / Q000494:pharmacology; D000975:Antioxidants / Q000009:adverse effects / Q000494:pharmacology; D015415:Biomarkers / Q000737:chemistry / Q000378:metabolism; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D007306:Insecticides / Q000633:toxicity; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects*; D051379:Mice; D047495:PPAR gamma / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014315:Triterpenes / Q000009:adverse effects / Q000494:pharmacology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D019440:Anti-Obesity Agents; D000972:Antineoplastic Agents, Phytogenic; D000975:Antioxidants; D015415:Biomarkers; D022763:CCAAT-Enhancer-Binding Protein-alpha; D007306:Insecticides; D047495:PPAR gamma; D053978:Pentacyclic Triterpenes; D012333:RNA, Messenger; D014315:Triterpenes; C050414:celastrol
keywords: Adipocytes differentiation; C/EBPα; Celastrol; Lipolysis; PPARγ(2)