Antioxidant catalase rescues against high fat diet-induced cardiac dysfunction via an IKKβ-AMPK-dependent regulation of autophagy

• Published in: Biochimica et biophysica acta 2015-02, Vol.1852 (2), p.343-352
• Main Authors: Liang, Lei, Shou, Xi-Ling, Zhao, Hai-Kang, Ren, Gu-qun, Wang, Jian-Bang, Wang, Xi-Hui, Ai, Wen-Ting, Maris, Jackie R., Hueckstaedt, Lindsay K., Ma, Ai-qun, Zhang, Yingmei
• Format: Article
• Language: English
• Subjects: AMP-Activated Protein Kinases - metabolism; AMPK; Animals; Antioxidants - metabolism; Autophagy; Autophagy - drug effects; Calcium - metabolism; Cardiomegaly - enzymology; Cardiomegaly - pathology; Cardiomegaly - physiopathology; Cardiomyocyte; Catalase; Catalase - metabolism; Diet, High-Fat; Echocardiography; Fat diet; Feeding Behavior - drug effects; Heart - drug effects; Heart - physiopathology; I-kappa B Kinase - metabolism; IKKβ; Intracellular Space - metabolism; Male; Mice, Transgenic; Models, Biological; Myocardial Contraction - drug effects; Palmitic Acid - pharmacology; Reactive Oxygen Species - metabolism; Signal Transduction - drug effects
• ISSN: 0925-4439; 0006-3002; 1879-260X
• DOI: 10.1016/j.bbadis.2014.06.027

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 20weeks 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. •We examine the impact of catalase on high fat diet-induced changes in cardiac function.•Catalase alleviates high fat diet-induced cardiac geometric and functional anomalies.•Catalase preserves high fat diet-induced suppression of autophagy.