title: Phosphoprotein phosphatase 1CB (PPP1CB), a novel adipogenic activator, promotes 3T3-L1 adipogenesis.
abstract: Understanding the molecular networks that regulate adipogenesis is crucial for gaining insight into obesity and identifying medicinal targets thereof is necessary for pharmacological interventions. However, the identity and molecular actions of activators that promote the early development of adipocytes are still largely unknown. Here, we demonstrate a novel role for phosphoprotein phosphatase 1CB (PPP1CB) as a potent adipogenic activator that promotes adipocyte differentiation. PPP1CB expression increased in vitro during the early phase of 3T3-L1 adipogenesis and in the murine model of high-fat diet-induced obesity. Depletion of PPP1CB dramatically suppressed the differentiation of 3T3-L1 cells into mature adipocytes, with a concomitant change in adipocyte marker genes and significantly inhibited clonal expansion. We also showed that knockdown of PPP1CB caused a significant decrease in C/EBPδ expression, which in turn resulted in attenuation of PPARγ, C/EBPα, adiponectin, and aP2. In addition, we elucidated the functional significance of PPP1CB by linking p38 activation to C/EBPδ expression in early adipogenesis. Overall, our findings demonstrate a novel function of PPP1CB in promoting adipogenesis and suggest that PPP1CB may be a promising therapeutic target for treatment of obesity and obesity-related diseases.
authors.affiliation: Department of Chemistry, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Young-Lai
authors.initials: YL
authors.lastname: Cho
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea; Department of Biomolecular Science, University of Science & Technology, Daejeon, Republic of Korea.
authors.forename: Jeong-Ki
authors.initials: JK
authors.lastname: Min
authors.affiliation: Department of Chemistry, Dongguk University, Seoul 100-715, Republic of Korea.
authors.forename: Kyung Min
authors.initials: KM
authors.lastname: Roh
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Won Kon
authors.initials: WK
authors.lastname: Kim
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Baek Soo
authors.initials: BS
authors.lastname: Han
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Kwang-Hee
authors.initials: KH
authors.lastname: Bae
authors.affiliation: Functional Genomics Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Republic of Korea.
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Lee
authors.affiliation: Department of Chemistry, Dongguk University, Seoul 100-715, Republic of Korea; Research Institute of Biomolecular Chemistry, Dongguk University, Seoul 100-715, Republic of Korea. Electronic address: sjchung@dongguk.edu.
authors.forename: Sang J
authors.initials: SJ
authors.lastname: Chung
authors.affiliation: Research Institute of Biomolecular Chemistry, Dongguk University, Seoul 100-715, Republic of Korea. Electronic address: jin0305@dongguk.edu.
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Kang
mesh_terms: D041721:3T3-L1 Cells; D017667:Adipocytes / Q000201:enzymology* / Q000473:pathology; D050156:Adipogenesis / Q000235:genetics*; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism; D000818:Animals; D051743:CCAAT-Enhancer-Binding Protein-delta / Q000235:genetics / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation; D059305:Diet, High-Fat; D004041:Dietary Fats / Q000008:administration & dosage*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000201:enzymology / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D054645:Protein Phosphatase 1 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D052242:Adiponectin; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C497253:Cebpd protein, mouse; D004041:Dietary Fats; C524662:FABP4 protein, rat; D050556:Fatty Acid-Binding Proteins; D034741:RNA, Small Interfering; D051743:CCAAT-Enhancer-Binding Protein-delta; D048051:p38 Mitogen-Activated Protein Kinases; D054645:Protein Phosphatase 1
keywords: 3T3-L1 preadipocyte; Adipogenesis; C/EBPδ; Phosphoprotein phosphatase 1CB; p38