Sitagliptin mitigates oxidative stress and up-regulates mitochondrial biogenesis markers in Brown adipose tissues of high-fat diet fed obese mice through AMPK phosphorylation

Abstract

Aims: The present study was designed to investigate the effects of Sitagliptin (SGN) on oxidative stress, 5' adenosine monophosphate-activated protein kinase (AMPK) phosphorylation, together with mitochondrial biogenesis and thermogenic markers in intercapsular brown adipose tissue (iBAT) of Swiss albino mice fed high-fat diet for sixteen weeks. Methods: Mice were distributed into five groups with last eight weeks of treatment: Normal control (NC): control diet with regular drinking water; Obese control (OC): 60% high-fat diet with 20% fructose drinking water (HFFR); Treatment-1: (OC + MET): HFFR with metformin (MET) 100 mg/kg/day; Treatment-2 (OC + SGN30): HFFR with SGN 30 mg/kg/day; Treatment-3 (OC + SGN20): HFFR with SGN 20 mg/kg/day. Fasting blood glucose, serum free fatty acid and adiponectin levels were measured. Oxidative stress, P-AMPK protein expression and mRNA expression of PPARα, PGC1-α, NRF-1, TFAM, and UCP-1 in iBAT were studied. Results: SGN treatment for eight weeks ameliorated oxidative stress, improved P-AMPK protein expression and enhanced mitochondrial biogenesis and thermogenic mediators in iBAT. Conclusion: The findings from the present study suggest the beneficial role of SGN in ameliorating obesity associated oxidative stress and up-regulated mitochondrial biogenesis and thermogenic markers in iBAT of obese mice, possibly through AMPK activation. © 2020