title: Irisin improves perivascular adipose tissue dysfunction via regulation of the heme oxygenase-1/adiponectin axis in diet-induced obese mice.
abstract: OBJECTIVE
  To determine whether irisin could improve perivascular adipose tissue (PVAT) dysfunction via regulation of the heme oxygenase-1 (HO-1)/adiponectin axis in obesity.
  
  
  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-α 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-α 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-α expression in PVAT. Irisin treatment enhanced brown adipocyte markers UCP-1 and Cidea expression in PVAT from HFD mice.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Ningning
authors.initials: N
authors.lastname: Hou
authors.affiliation: Department of Radiotherapy, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Yihui
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Han
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Di
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Xiaoshuang
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China.
authors.forename: Shuting
authors.initials: S
authors.lastname: Hou
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Weifang Medical University, Weifang, China. Electronic address: sxdfriend@sina.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D052242:Adiponectin / Q000378:metabolism*; D000273:Adipose Tissue / Q000378:metabolism* / Q000503:physiopathology*; D000818:Animals; D001011:Aorta / Q000378:metabolism; D015415:Biomarkers; D059305:Diet, High-Fat / Q000009:adverse effects; D005353:Fibronectins / Q000378:metabolism* / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D051379:Mice; D008820:Mice, Obese; D009765:Obesity / Q000209:etiology / Q000378:metabolism; D018384:Oxidative Stress; D013481:Superoxides / Q000378:metabolism
chemical_list: D052242:Adiponectin; D015415:Biomarkers; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D013481:Superoxides; D051547:Heme Oxygenase-1
keywords: Adiponectin; Heme oxygenase-1; Irisin; Perivascular adipose tissue