期刊
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
卷 396, 期 4, 页码 1054-1059出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2010.05.064
关键词
Adipogenesis; PDE5 inhibitor; PKG; Adipocytes
资金
- National High Technology Research and Development Program of China (863 Program) [2007AA02Z301]
- National Science and Technology Major Project [2009ZX09301-001]
- Shanghai Science and Technology Innovation Program [08431900800]
- State Key Program of Basic Research of China [2009CB918502]
Sildenafil is the first oral PDE5 inhibitor for the treatment of erectile dysfunction and pulmonary arterial hypertension. In the present study, we investigated the effect of sildenafil on adipogenesis in 3T3L1 pre-adipocytes. Treatment with sildenafil for 8 days significantly promoted adipogenesis characterized by increased lipid droplet and triglyceride content in 3T3L1 cells. Meanwhile, sildenafil induced a pronounced up-regulation of the expression of adipocyte-specific genes, such as aP2 and GLUT4. The results by RT-PCR and Western blotting further showed that sildenafil increased the sequential expression of C/EBP beta, PPAR gamma and C/E8P alpha. Additionally, we found that the other two PDE5 inhibitors (vardenafil and tadalafil) and the cGMP analog 8-pCPT-cGMP also increased adipogenesis. Likewise, 8-pCPT-cGMP could upregulate the expression of adipogenic and adipocyte-specific genes. Importantly, the PKG inhibitor Rp-8pCPT-cGMP was able to inhibit both sildenafil and 8-pCPT-cGMP-induced adipogenesis. Furthermore, sildenafil promoted basal and insulin-mediated glucose uptake in 3T3L1 cells, which was counteracted by Rp-8-pCPT-cGMP. These results indicate that sildenafil could promote adipogenesis accompanied by increased glucose uptake through a PKG pathway at least partly. (C) 2010 Elsevier Inc. All rights reserved.
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