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| Content Provider | PubMed Central |
|---|---|
| Author | Samira, Fargali Scherer, Thomas Shin, Andrew C. Sadahiro, Masato Buettner, Christoph Salton, Stephen R. |
| Abstract | Targeted deletion of VGF, a neuronal and endocrine secreted protein and neuropeptide precursor, produces a lean, hypermetabolic mouse that is resistant to diet-, lesion-, and genetically-induced obesity and diabetes. We hypothesized that increased sympathetic nervous system activity in Vgf−/Vgf− knockout mice is responsible for increased energy expenditure and decreased fat storage, and that increased beta-adrenergic receptor stimulation induces lipolysis in white adipose tissue (WAT) of Vgf−/Vgf− mice. We found that fat mass was markedly reduced in Vgf−/Vgf− mice. Within knockout WAT, phosphorylation of protein kinase A (PKA) substrate increased in males and females, phosphorylation of hormone sensitive lipase (HSL) (Ser563) increased in females, and levels of adipose triglyceride lipase (ATGL), comparative gene identification-58 (CGI-58), and phospho-perilipin, were higher in male Vgf−/Vgf− WAT compared to wild type, consistent with increased lipolysis. The phosphorylation of AMP-activated protein kinase (AMPK) (Thr172) and levels of the AMPK kinase, transforming growth factor β-activated kinase 1 (TAK-1), were decreased. This was associated with a decrease in HSL Ser565 phosphorylation, the site phosphorylated by AMPK, in both male and female Vgf−/Vgf− WAT. No significant differences in phosphorylation of cAMP response element binding protein (CREB) or the p42/44 mitogen-activated protein kinase (MAPK) were noted. Despite this evidence supporting increased cAMP signaling and lipolysis, lipogenesis as assessed by fatty acid synthase (FAS) protein expression and phosphorylated acetyl-CoA carboxylase (pACC) was not decreased. Our data suggest that the VGF precursor or selected VGF-derived peptides dampen sympathetic outflow pathway activity to WAT to regulate fat storage and lipolysis. |
| Related Links | http://dx.doi.org/10.1530/joe-12-0172 |
| Ending Page | 322 |
| Page Count | 10 |
| Starting Page | 313 |
| File Format | |
| ISSN | 00220795 |
| e-ISSN | 14796805 |
| Journal | The Journal of endocrinology |
| Issue Number | 2 |
| Volume Number | 215 |
| Language | English |
| Publisher Date | 2012-11-01 |
| Access Restriction | Open |
| Subject Keyword | Medicine(all) Research in Higher Education |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Endocrinology |
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