Sildenafil induces browning of subcutaneous white adipose tissue in overweight adults

• Published in: Metabolism, clinical and experimental Vol. 78; pp. 106 - 117
• Main Authors: Li, Shuguang, Li, Yixiang, Xiang, Lin, Dong, Jing, Liu, Min, Xiang, Guangda
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.01.2018
• Subjects: Adipocytes - drug effects; Adipocytes - metabolism; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; Adult; Animals; Browning of white adipose; Catecholamines - metabolism; Cell Adhesion Molecules - metabolism; Cyclic GMP-Dependent Protein Kinase Type I - metabolism; Double-Blind Method; Human adult; Humans; Male; Mice; Mice, Inbred C57BL; Microfilament Proteins - metabolism; Mitochondria - drug effects; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Obesity - drug therapy; Obesity - metabolism; Overweight - drug therapy; Overweight - metabolism; Phosphodiesterase type-5 inhibitor; Phosphoproteins - metabolism; Signal Transduction - drug effects; Sildenafil Citrate - therapeutic use; Subcutaneous Fat - drug effects; Subcutaneous Fat - metabolism; Uncoupling Protein 1 - metabolism; Vasodilator-Stimulated Phosphoprotein; Young Adult; Human adult; sWAT; fT3; LDL-C; cGMP; FBG; WAT; HDL-C; MYDGF; Browning of white adipose; PRDM16; mTOR; FMD; LC3; FGF21; VASP; PDE5i; DIO2; PGC-1α; UCP-1; Phosphodiesterase type-5 inhibitor; IL-6; TC; S6K1; iWAT; TNF-α; ADRB3; BAT; RMR
• ISSN: 0026-0495; 1532-8600; 1532-8600
• DOI: 10.1016/j.metabol.2017.09.008

To investigate that short-term treatment of sildenafil can induce browning of subcutaneous white adipose tissue (sWAT) in human adults. A randomized, double-blinded, placebo-controlled, parallel group trial. Sixteen eligibility overweight male subjects were recruited, comparing 100mg/day sildenafil versus an identical placebo therapy for 7days. sWAT samples were collected from subjects before and after 7-day sildenafil or placebo interventions. The results showed that multilocular UCP1-positive adipocytes existed in sWAT samples from subjects after sildenafil treatment. Compared to before treatment in both group as well as after treatment in placebo, sildenafil significantly decreased adipocyte size, increased the expressions of UCP1 protein and mRNA, mitochondrial density, and leak respiratory capacity in sWAT (p<0.05). Sildenafil also increased plasma cyclic guanosine-3′,5′-monophosphate (cGMP) and catecholamine concentrations (p<0.05), and consequently activated the expressions of vasodilator-stimulated phosphoprotein (VASP) and p70 ribosomal S6 kinase 1 (S6K1) (p<0.05). Sildenafil did not activate typical brown fat. The current findings demonstrate that sildenafil can induce browning of sWAT in human, and this action may be through cGMP-dependent protein kinase I and mechanistic/mammalian target of rapamycin (mTOR) signaling pathways. Sldenafil may be a promising treatment for metabolic disease.