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