Sildenafil promotes adipogenesis through a PKG pathway.
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 preadipocytes. 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/EBP 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 up-regulate the expression of adipogenic and adipocyte-specific genes. Importantly, the PKG inhibitor Rp-8-pCPT-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.
Zhang
Xiaodong
X
Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, Zhang Jiang Hi-Tech Park, Pudong, Shanghai 201203, China.
Ji
Jun
J
Yan
Guirui
G
Wu
Jingwei
J
Sun
Xiaoyun
X
Shen
Jingshan
J
Jiang
Hualiang
H
Wang
Heyao
H
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D050156:Adipogenesis / Q000187:drug effects*; D000818:Animals; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D017869:Cyclic GMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D050556:Fatty Acid-Binding Proteins / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics; D007328:Insulin / Q000494:pharmacology; D051379:Mice; D047495:PPAR gamma / Q000235:genetics; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011687:Purines / Q000494:pharmacology; D000068677:Sildenafil Citrate; D013450:Sulfones / Q000494:pharmacology*; D013873:Thionucleotides / Q000494:pharmacology
C090860:8-(4-chlorophenylthio)guanosine 3',5'-cyclic monophosphorothioate; D022782:CCAAT-Enhancer-Binding Protein-beta; D022762:CCAAT-Enhancer-Binding Proteins; C530718:CEBPA protein, mouse; C545013:Cebpb protein, mouse; C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D051275:Glucose Transporter Type 4; D007328:Insulin; D047495:PPAR gamma; D058986:Phosphodiesterase 5 Inhibitors; D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D013873:Thionucleotides; D000068677:Sildenafil Citrate; D017869:Cyclic GMP-Dependent Protein Kinases; D006152:Cyclic GMP; D005947:Glucose