title: Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy.
abstract: Autophagy, a conservative degradation process for long-lived and damaged proteins, participates in a variety of biological processes including obesity. However, the precise mechanism of action behind obesity-induced changes in autophagy still remains elusive. This study was designed to examine the role of the antioxidant catalase in high fat diet-induced changes in cardiac geometry and function as well as the underlying mechanism of action involved with a focus on autophagy. Wild-type (WT) and transgenic mice with cardiac overexpression of catalase were fed low or high fat diet for 20 weeks prior to assessment of myocardial geometry and function. High fat diet intake triggered obesity, hyperinsulinemia, and hypertriglyceridemia, the effects of which were unaffected by catalase transgene. Myocardial geometry and function were compromised with fat diet intake as manifested by cardiac hypertrophy, enlarged left ventricular end systolic and diastolic diameters, fractional shortening, cardiomyocyte contractile capacity and intracellular Ca²⁺ mishandling, the effects of which were ameliorated by catalase. High fat diet intake promoted reactive oxygen species production and suppressed autophagy in the heart, the effects of which were attenuated by catalase. High fat diet intake dampened phosphorylation of inhibitor kappa B kinase β(IKKβ), AMP-activated protein kinase (AMPK) and tuberous sclerosis 2 (TSC2) while promoting phosphorylation of mTOR, the effects of which were ablated by catalase. In vitro study revealed that palmitic acid compromised cardiomyocyte autophagy and contractile function in a manner reminiscent of fat diet intake, the effect of which was significantly alleviated by inhibition of IKKβ, activation of AMPK and induction of autophagy. Taken together, our data revealed that the antioxidant catalase counteracts against high fat diet-induced cardiac geometric and functional anomalies possibly via an IKKβ-AMPK-dependent restoration of myocardial autophagy. This article is part of a Special Issue entitled: Autophagy and protein quality control in cardiometabolic diseases.
authors.affiliation: Department of Cardiology, The People's Hospital of Shaanxi Province, Xi'an, China; Department of Cardiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Liang
authors.affiliation: Department of Cardiology, The People's Hospital of Shaanxi Province, Xi'an, China; Department of Cardiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Xi-Ling
authors.initials: XL
authors.lastname: Shou
authors.affiliation: Department of Neurosurgery, The Second Affiliated Hospital, Xi'an Medical University, Xi'an, China.
authors.forename: Hai-Kang
authors.initials: HK
authors.lastname: Zhao
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Medical University, Xi'an, China.
authors.forename: Gu-Qun
authors.initials: GQ
authors.lastname: Ren
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Medical University, Xi'an, China.
authors.forename: Jian-Bang
authors.initials: JB
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The Second Affiliated Hospital, Xi'an Medical University, Xi'an, China.
authors.forename: Xi-Hui
authors.initials: XH
authors.lastname: Wang
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Wen-Ting
authors.initials: WT
authors.lastname: Ai
authors.affiliation: Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
authors.forename: Jackie R
authors.initials: JR
authors.lastname: Maris
authors.affiliation: Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA.
authors.forename: Lindsay K
authors.initials: LK
authors.lastname: Hueckstaedt
authors.affiliation: Department of Cardiology, The First Affiliated Hospital, School of Medicine, Xi'an Jiaotong University, Xi'an, China. Electronic address: maaiqun@medmail.com.cn.
authors.forename: Ai-Qun
authors.initials: AQ
authors.lastname: Ma
authors.affiliation: Center for Cardiovascular Research and Alternative Medicine, University of Wyoming College of Health Sciences, Laramie, WY 82071, USA. Electronic address: zhangym197951@126.com.
authors.forename: Yingmei
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001343:Autophagy / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D006332:Cardiomegaly / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D002374:Catalase / Q000378:metabolism*; D059305:Diet, High-Fat; D004452:Echocardiography; D005247:Feeding Behavior / Q000187:drug effects; D006321:Heart / Q000187:drug effects / Q000503:physiopathology*; D051550:I-kappa B Kinase / Q000378:metabolism*; D042541:Intracellular Space / Q000378:metabolism; D008297:Male; D008822:Mice, Transgenic; D008954:Models, Biological; D009200:Myocardial Contraction / Q000187:drug effects; D019308:Palmitic Acid / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000975:Antioxidants; D017382:Reactive Oxygen Species; D019308:Palmitic Acid; D002374:Catalase; D051550:I-kappa B Kinase; D055372:AMP-Activated Protein Kinases; D002118:Calcium
keywords: AMPK; Autophagy; Cardiomyocyte; Catalase; Fat diet; IKKβ