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.
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Abbreviations
- AD:
-
Alzheimer’s disease
- Akt:
-
Protein kinase B
- aP2:
-
Adipocyte protein 2
- C/EBPα:
-
CCAAT-enhancer-binding protein α
- DMI:
-
Dexamethasone, 1-methyl-3-isobutylxanthine and insulin
- HFD:
-
High-fat diet
- IRES:
-
Internal ribosome entry sequence
- MMPs:
-
Matrix metalloproteinases
- NEP:
-
Neprilysin, neutral endopeptidase, EC3.4.24.11
- PI3K:
-
Phosphatidylinositol 3-kinase
- PPARγ:
-
Peroxisome proliferator-activated receptor γ
- qRT-PCR:
-
Quantitative real-time PCR
- SD:
-
Standard chow diet
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Acknowledgements
This research was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning (#2015R1A2A2A01005687).
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Kim, J., Han, D., Byun, SH. et al. Neprilysin facilitates adipogenesis through potentiation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway. Mol Cell Biochem 430, 1–9 (2017). https://doi.org/10.1007/s11010-017-2948-6
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DOI: https://doi.org/10.1007/s11010-017-2948-6