title: Perivascular fat-mediated vascular dysfunction and remodeling through the AMPK/mTOR pathway in high-fat diet-induced obese rats.
abstract: Perivascular adipose tissue (PVAT) is implicated in the regulation of vascular function in the physiological state, but the modulatory effect of PVAT on vasculature during obesity is poorly understood. Endothelial nitric oxide synthase (eNOS), AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) participate in the regulation of vascular function. We therefore investigated whether PVAT has a potential role through the AMPK/mTOR pathway in obesity-related vascular dysfunction. Wistar rats on a high-fat diet (HFD) for 6 months had higher periaortic fat mass compared with rats on a chow diet (3.31+/-0.56 vs. 2.34+/-0.28 g, P<0.05). Obesity-related impairment of endothelium-dependent relaxation of the aorta was markedly attenuated by temporary periaortic fat removal whereas obesity-related enhancement of contractile performance was unaffected. Rats on an HFD had thicker aortic tunica medias (180.06+/-7.56 vs. 128.14+/-13.21 microm for rats on a chow diet, P<0.01) and larger periaortic adipocytes than rats on a chow diet (1209.00+/-62.65 vs. 447.20+/-21.31 microm(2), respectively, P<0.01). Furthermore, mesenteric arterial rings incubated with periaortic fat from rats on an HFD demonstrated lower endothelium-dependent relaxation. This effect was absent in mesenteric arterial rings incubated with periaortic fat from rats on a chow diet. Moreover, an HFD led to a downregulation of AMPK and eNOS in the aorta with a concurrent upregulation of mTOR. In a parallel in vitro study, culturing vascular smooth muscle cells with periaortic adipocytes from rats on an HFD reduced the AMPK phosphorylation and increased mTOR phosphorylation, and the latter one was blocked by the incubation of compound C. We conclude that PVAT likely impacts obesity-related vascular dysfunction and remodeling through impairment of eNOS-mediated vasodilatation and the AMPK/mTOR pathway.
authors.affiliation: Department of Hypertension and Endocrinology, Center for Hypertension and Metabolic Diseases, Chongqing Institute of Hypertension, Daping Hospital, Third Military Medical University, Chongqing, PR China.
authors.forename: Liqun
authors.initials: L
authors.lastname: Ma
authors.forename: Shuangtao
authors.initials: S
authors.lastname: Ma
authors.forename: Hongbo
authors.initials: H
authors.lastname: He
authors.forename: Dachun
authors.initials: D
authors.lastname: Yang
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Chen
authors.forename: Zhidan
authors.initials: Z
authors.lastname: Luo
authors.forename: Daoyan
authors.initials: D
authors.lastname: Liu
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Zhu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004041:Dietary Fats; D050152:Intra-Abdominal Fat / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction / Q000502:physiology; D058570:TOR Serine-Threonine Kinases; D017540:Tunica Media / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D014664:Vasodilation / Q000502:physiology
chemical_list: D004041:Dietary Fats; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D058570:TOR Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases