title: Neprilysin facilitates adipogenesis through potentiation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway.
abstract: Neprilysin (NEP) is a zinc metallopeptidase that cleaves a number of small peptides into inactive forms. Despite the recent evidence of a significant correlation between the levels of NEP in plasma and the severity of obesity in humans, a cause-and-effect relationship or a functional role of NEP in obesity has remained uncertain. In this study, we show that NEP has a positive regulatory effect on fat cell formation from precursor cells. NEP increases the accumulation of cytoplasmic triglycerides in 3T3-L1 preadipocytes or the C3H10T1/2 mesenchymal stem cell line in differentiation conditions. Consistently, cells expressing NEP showed an increase in mRNA expression of adipogenic transcription factors, peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and the adipocyte markers aP2 and adipsin. Furthermore, this NEP-enhanced induction of adipogenesis was found to require the enzymatic activity of NEP, leading to augmentation of the phosphatidylinositol 3-kinase (PI3K)-protein kinase B (Akt) signaling pathway. In summary, our results indicate that NEP accelerates adipogenesis through enhancement of insulin-mediated PI3K-Akt activation and imply a high therapeutic value of NEP in treating obesity and obesity-related disorders.
authors.affiliation: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea.
authors.forename: Juwan
authors.initials: J
authors.lastname: Kim
authors.affiliation: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea.
authors.forename: Dasol
authors.initials: D
authors.lastname: Han
authors.affiliation: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea.
authors.forename: Sung-Hyun
authors.initials: SH
authors.lastname: Byun
authors.affiliation: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea.
authors.forename: Mookwang
authors.initials: M
authors.lastname: Kwon
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Osong, Chungcheongbuk-do, 28159, South Korea.
authors.forename: Sun-Jung
authors.initials: SJ
authors.lastname: Cho
authors.affiliation: Division of Brain Diseases, Center for Biomedical Sciences, Korea National Institute of Health, Osong, Chungcheongbuk-do, 28159, South Korea.
authors.forename: Young Ho
authors.initials: YH
authors.lastname: Koh
authors.affiliation: College of Biotechnology and Bioengineering, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, South Korea. keejung@skku.edu.
authors.forename: Keejung
authors.identifier: http://orcid.org/0000-0002-2361-9039
authors.initials: K
authors.lastname: Yoon
mesh_terms: D041721:3T3-L1 Cells; D050156:Adipogenesis; D000818:Animals; D022762:CCAAT-Enhancer-Binding Proteins / Q000378:metabolism; D051379:Mice; D015260:Neprilysin / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; D047495:PPAR gamma; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D015260:Neprilysin
keywords: Adipogenesis; Akt; Metabolic syndrome; Neprilysin; PI3K