Neprilysin facilitates adipogenesis through potentiation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway

• DOI: 10.1007/s11010-017-2948-6
• Publication Date: 2017-02-27T02:32:41Z
• Authors: Juwan Kim; Dasol Han; Sung-Hyun Byun; Mookwang Kwon; Sun-Jung Cho; Young Ho Koh; Keejung Yoon
• Keywords: 2. Zero hunger; 0303 health sciences; Adipogenesis; PPAR gamma; Mice; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; 3T3-L1 Cells; CCAAT-Enhancer-Binding Proteins; Animals; Neprilysin; Proto-Oncogene Proteins c-akt; Signal Transduction

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.