title: Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway.
abstract: Irisin is a novel hormone secreted by myocytes. Lower levels of irisin are independently associated with endothelial dysfunction in obese subjects. The objective of this study was to explore whether irisin exerts a direct vascular protective effect on endothelial function in high-fat-diet-induced obese mice. Male C57BL/6 mice were given chow or a high-fat diet with or without treatment with irisin. Aortic endothelial function was determined by measuring endothelium-dependent vasodilatation (EDV). Nitric oxide (NO) in the aorta was determined. The effect of irisin on the levels of AMP-activated protein kinase (AMPK), Akt, and endothelial NO synthase (eNOS) phosphorylation in endothelial cells was determined. Human umbilical vein endothelial cells were used to study the role of irisin in the AMPK-eNOS pathway. Acetylcholine-stimulated EDV was significantly lower in obese mice compared with control mice. Treatment of obese mice with irisin significantly enhanced EDV and improved endothelial function. This beneficial effect of irisin was partly attenuated in the presence of inhibitors of AMPK, Akt, and eNOS. Treatment of obese mice with irisin enhanced NO production and phosphorylation of AMPK, Akt, and eNOS in endothelial cells. These factors were also enhanced by irisin in human umbilical vein endothelial cells in vitro. Suppression of AMPK expression by small interfering RNA blocked irisin-induced eNOS and Akt phosphorylation and NO production. We have provided the first evidence that irisin improves endothelial function in aortas of high-fat-diet-induced obese mice. The mechanism for this protective effect is related to the activation of the AMPK-eNOS signaling pathway.
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 Magnetic Resonance Imaging, Medical Imaging Center, Affiliated Hospital of Weifang Medical University, Weifang, China; and.
authors.forename: Shuxian
authors.initials: S
authors.lastname: Zhang
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 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 sxdfriend@sina.com.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Sun
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D059305:Diet, High-Fat; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D005353:Fibronectins / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction; D014664:Vasodilation / Q000187:drug effects*
chemical_list: C577593:FNDC5 protein, human; C571428:FNDC5 protein, mouse; D005353:Fibronectins; D009569:Nitric Oxide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases
keywords: endothelial function; irisin; nitric oxide; obesity