title: Coprinus comatus cap inhibits adipocyte differentiation via regulation of PPARγ and Akt signaling pathway.
abstract: This study assessed the effects of Coprinus comatus cap (CCC) on adipogenesis in 3T3-L1 adipocytes and the effects of CCC on the development of diet-induced obesity in rats. Here, we showed that the CCC has an inhibitory effect on the adipocyte differentiation of 3T3-L1 cells, resulting in a significant decrease in lipid accumulation through the downregulation of several adipocyte specific-transcription factors, including CCAAT/enhancer binding protein β, C/EBPδ, and peroxisome proliferator-activated receptor gamma (PPARγ). Moreover, treatment with CCC during adipocyte differentiation induced a significant down-regulation of PPARγ and adipogenic target genes, including adipocyte protein 2, lipoprotein lipase, and adiponectin. Interestingly, the CCC treatment of the 3T3-L1 adipocytes suppressed the insulin-stimulated Akt and GSK3β phosphorylation, and these effects were stronger in the presence of an inhibitor of Akt phosphorylation, LY294002, suggesting that CCC inhibited adipocyte differentiation through the down-regulation of Akt signaling. In the animal study, CCC administration significantly reduced the body weight and adipose tissue weight of rats fed a high fat diet (HFD) and attenuated lipid accumulation in the adipose tissues of the HFD-induced obese rats. The size of the adipocyte in the epididymal fat of the CCC fed rats was significantly smaller than in the HFD rats. CCC treatment significantly reduced the total cholesterol and triglyceride levels in the serum of HFD rats. These results strongly indicated that the CCC-mediated decrease in body weight was due to a reduction in adipose tissue mass. The expression level of PPARγ and phospho-Akt was significantly lower in the CCC-treated HFD rats than that in the HFD obesity rats. These results suggested that CCC inhibited adipocyte differentiation by the down-regulation of major transcription factor involved in the adipogenesis pathway including PPARγ through the regulation of the Akt pathway in 3T3-L1 cells and HFD adipose tissue.
authors.affiliation: Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Hyoung Joon
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Molecular Science and Technology, Ajou University, Suwon, Korea.
authors.forename: Jisoo
authors.initials: J
authors.lastname: Yun
authors.affiliation: Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Sun-Hee
authors.initials: SH
authors.lastname: Jang
authors.affiliation: Department of Animal Science & Biotechnology, Gyeongnam National University of Science and Technology, Jinju, Korea.
authors.forename: Suk Nam
authors.initials: SN
authors.lastname: Kang
authors.affiliation: Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Beong-Sam
authors.initials: BS
authors.lastname: Jeon
authors.affiliation: Animal Genetic Resources Station, National Institute of Animal Science, RDA, Namwon, Korea.
authors.forename: Yeoung-Gyu
authors.initials: YG
authors.lastname: Ko
authors.affiliation: Department of Environmental Health Science, New York Medical College, Valhalla, New York, United States of America.
authors.forename: Hong-Duck
authors.initials: HD
authors.lastname: Kim
authors.affiliation: Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Chung-Kil
authors.initials: CK
authors.lastname: Won
authors.affiliation: Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Gon-Sup
authors.initials: GS
authors.lastname: Kim
authors.affiliation: Institute of Life Science, College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea.
authors.forename: Jae-Hyeon
authors.initials: JH
authors.lastname: Cho
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects / Q000235:genetics; D050154:Adiposity / Q000187:drug effects; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects*; D002784:Cholesterol / Q000097:blood; D045424:Complex Mixtures / Q000494:pharmacology* / Q000627:therapeutic use; D003302:Coprinus / Q000737:chemistry*; D059305:Diet, High-Fat; D015536:Down-Regulation / Q000187:drug effects; D005419:Flavonoids / Q000032:analysis; D016166:Free Radical Scavengers / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D009765:Obesity / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D047495:PPAR gamma / Q000378:metabolism*; D010636:Phenols / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000097:blood
chemical_list: D045424:Complex Mixtures; D005419:Flavonoids; D016166:Free Radical Scavengers; D047495:PPAR gamma; D010636:Phenols; D012333:RNA, Messenger; D014157:Transcription Factors; D014280:Triglycerides; D002784:Cholesterol; D000071679:Glycogen Synthase Kinase 3 beta; C000605507:Gsk3b protein, mouse; C000605508:Gsk3b protein, rat; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3; D005947:Glucose