Anti-adiposity impact of phosphodiesterase-5 inhibitor, Sildenafil is possibly through browning of white adipose tissue and FGF21 in obese rats

Abstract

Background & Aim: Fibroblast growth factor 21 (FGF21) is a peptide hormone recently discovered to be released from brown adipocytes. It plays an outstanding role in the metabolic homeostasis. Induction of brown-like adipocytes termed beige/brite within the white adipose tissue (WAT) by means of browning agents is known as "browning process". These beige/brite cells due to plenty of mitochondria and unique expression of uncoupling protein-1 (UCP1), promotes energy expenditure. Being the WAT is excessively expanded in adiposity, the browning agents have gained great interest to combat obesity. The browning effect of Sildenafil (Sild) in obese rats stills a matter of debate. So, we aimed to illustrate it. Method & Results: 3 groups of rats were conducted; control group fed standard diet for 9 weeks, obese non-treated group fed high-fat diet (HFD)-fed group for 9 weeks, and Sild-treated group fed HFD for 9 weeks and received Sild (20 mg /kg/s.c./each) twice daily in the last 3 weeks. Our findings revealed Sild reduced weight gain, fat depots weight, and adiposity index in spite of unchanged food intake. Additionally, it reduced serum triglycerides, free fatty acids, glucose, insulin, and insulin resistance index. The subcutaneous WAT of Sild-treated rats exhibited augmented UCP1, citrate synthase activity, and FGF21 and FGF21-Receptor1 expressions with the highest FGF21 serum levels. Conclusions: the present study suggested a protective impact of Sild against adiposity and insulin resistance through browning of WAT with enhanced FGF21-Receptor1 expression.