Exercise Prevents High-Fat Diet–Induced Impairment of Insulin-Induced Vasodilatation of Muscle Arterioles in Mice by Browning Perivascular Adipose Tissue of Mice

Abstract

Perivascular adipose tissue (PVAT) surrounds most arteries and enhances insulin-induced vasodilatation through local release of adipokines. Obesity impairs the vasoregulatory function of PVAT on insulin-induced vasodilation, thus contributing to cardiovascular risk. Exercise enhances insulin-induced vasodilatation, and we evaluated whether exercise preconditions the muscle microcirculation against HFD-induced impairment of insulin-induced vasodilatation. C57BL/6 mice were exercised for 4 weeks (EX), or fed a high fat diet (HFD) for 2 weeks. Exercise preconditioning was performed by exercising mice for 4 weeks prior to HFD treatment (EX+HFD) or before and during HFD (EX+HFD/EX). HFD increased femoral PVAT and exercise attenuated this effect [(Control (C) 9±1mg vs. HFD 64±7mg - p<0.01) (EX+HFD 29±5mg; EX+HFD/EX 32±2mg; p<0.01 vs. HFD)]. Insulin-induced vasodilatation (0.5 IU/kg i.p.) was evaluated in vivo in the cremaster muscle. HFD inhibited insulin-induced vasodilatation [C 22±5% dilatation; HFD -11±4.3% dilatation, p<0.01 vs. C], but exercise precondition restored it [EX+HFD-24±5% and EX+HFD/EX-32±8.9% dilatation; p<0.05]. Browning of adipose tissue improves insulin sensitivity and adipokine secretion, and we observed browning by an increase in the mRNA of the browning marker Ucp-1 in aortic PVAT [72% increase in EX+HFD/EX vs. C p<0.01] and in brown adipose tissue [C 3±0.3; HFD 10±1; EX 8±0.9; *EX+HFD 19±2; *EX+HFD/EX 14±1.8; 2-Δct p<0.01 vs. C]. mRNA of the vasoprotective adipokine adiponectin was increased in PVAT of EX and EX+HFD/EX mice (p<0.vs. C, HFD and EX+HFD), while the inflammatory TNF-α was substantially decreased (HFD vs. C, EX+HFD and EX+HFD/EX vs. HFD; p<0.05). In conclusion, exercise reduces the HFD-induced increase in PVAT and preserves insulin-induced vasodilatation by increasing mitochondrial uncoupling and improving adipokine expression in PVAT. Disclosure B.C.S. Boa: None. F.M. Ferr o: None. I.M. Gonzaga: None. L.R. Pinto: None. V.W.M. van Hinsbergh: None. E.C. Eringa: None.