Irisin improves perivascular adipose tissue dysfunction via regulation of the heme oxygenase-1/adiponectin axis in diet-induced obese mice

Aims: To determine whether irisin could improve perivascular adipose tissue (PVAT) dysfunction via regulation of the heme oxygenase-1 (HO-1)/adiponectin axis in obesity. Materials and methods: C57BL/6 mice were given chow or a high-fat diet (HFD) with or without treatment with irisin. The concentration-dependent responses of the thoracic aorta with or without PVAT (PVAT+ or PVAT-) to phenylephrine were studied in an organ bath. Protein levels of HO-1 and adiponectin were determined by western blot. UCP-1, Cidea, and TNF-alpha gene expression in PVAT were analyzed by real-time PCR. Results: Treatment of obese mice with irisin improved glucose and lipid metabolism, reduced plasma levels of TNF-alpha and malondialdehyde, and increased plasma adiponectin levels (P < 0.01). The anti-contractile effects of PVAT were attenuated in HFD mice and this attenuation was restored in HFD mice treated with irisin (P < 0.05). Incubation of aortas (PVAT+) with the HO-1 inhibitor and adiponectin receptor blocking peptide in irisin-treated HFD mice abolished the beneficial effects of irisin on PVAT function. The same results were also observed in HFD mice treated with irisin ex vivo. Treatment of HFD mice with irisin significantly enhanced protein levels of HO-1 and adiponectin, and reduced superoxide production and TNF-alpha expression in PVAT. Irisin treatment enhanced brown adipocyte markers UCP-1 and Cidea expression in PVAT from HFD mice. Conclusion: Irisin improved the anti-contractile properties of PVAT from the thoracic aorta in diet-induced obese mice. The mechanism for protective effects of irisin appeared to be related to upregulation of the HO-1/adiponectin axis in PVAT and browning of PVAT. (C) 2016 Elsevier Ltd. All rights reserved.