Leptin gene transfer regulates fibromuscular development and lipid deposition in muscles via SIRT1, FOXO3a and PGC-1α in mice in vivo
Affiliations: Key Laboratory of Molecular Animal Nutrition of the Ministry of Education and Key Laboratory of Feed and Animal Nutrition of Zhejiang Province, Feed Science Institute, Zhejiang University, Hangzhou 310058, P.R. China, College of Biosystems Engineering and Food Science, Zhejiang University, Hangzhou 310058, P.R. China
- Published online on: May 25, 2011 https://doi.org/10.3892/ijmm.2011.711
- Pages: 617-623
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Leptin gene transfer in the liver by hydrodynamic-based gene delivery instead of peptide administration was used to investigate the effects of leptin on muscle mass accretion and lipid accumulation in muscles of wild-type mice. Food intake (P<0.01), body weight (P<0.01) and white adipose tissue (P<0.01) were significantly reduced in the leptin gene-treated group compared with the control group. Moreover, plasma leptin concentration was significantly increased after administration of the mouse leptin gene at a dose of 15 µg per mouse for 1 day (P<0.01) or 1 week (P<0.05). Furthermore, the mRNA abundance of myosin heavy chain type I (MyHC-I), myosin heavy chain type II (MyHC-IIa, MyHC-IIx), adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and lipoprotein lipase (LPL) genes in gastrocnemius muscle and extensor digitorum longus after administration of leptin for 1 week were significantly increased compared with the control group. Finally, we investigated the mechanism by which leptin gene transfer affects fibromuscular and fat deposition in muscle. Gene expression and protein levels of SIRT1, and proliferator-activated receptor-γ coactivator-1α (PGC-1α) were remarkably increased in extensor digitorum longus. On the other hand, PGC-1α and FOXO3a gene expression was observed to have significantly increased in gastrocnemius muscle. However, only changes in the protein levels of PGC-1α were observed (P<0.05). These results suggest that leptin may affect the growth and development of muscle, and fat deposition in wild-type mice via SIRT1 and FOXO3a and their downstream targets, including PGC-1α.