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

AimsThe 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. MethodsMice 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. ResultsSGN treatment for eight weeks ameliorated oxidative stress, improved P-AMPK protein expression and enhanced mitochondrial biogenesis and thermogenic mediators in iBAT. ConclusionThe 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.