Obesity-related cardiovascular diseases are associated with overactivation of the renin-angiotensin system (RAS). However, the underlying mechanisms remain elusive. In this study, we investigate the role of angiotensin II (Ang II) in high-fat diet (HFD)-induced cardiac dysfunction by focusing on cardiac glucose and lipid metabolism and energy supply. Ang II plays a role in cardiovascular regulation mainly by stimulating angiotensin II type 1 receptor (AT1R), among which AT1aR is the most important subtype in regulating the function of the cardiovascular system. AT1aR gene knockout (AT1aR ‒/‒) rats and wild-type (WT) rats are randomly divided into four groups and fed with either a normal diet (ND) or a HFD for 12 weeks. The myocardial lipid content, Ang II level and cardiac function are then evaluated. The expressions of a number of genes involved in glucose and fatty acid oxidation and mitochondrial dynamics are measured by quantitative polymerase chain reaction and western blot analysis. Our results demonstrate that AT1aR knockout improves HFD-induced insulin resistance and dyslipidemia as well as lipid deposition and left ventricular dysfunction compared with WT rats fed a HFD. In addition, after feeding with HFD, AT1aR ‒/‒ rats not only show further improvement in glucose and fatty acid oxidation but also have a reverse effect on increased mitochondrial fission proteins. In conclusion, AT1aR deficiency ameliorates HFD-induced cardiac dysfunction by enhancing glucose and fatty acid oxidation, regulating mitochondrial dynamics-related protein changes, and further promoting cardiac energy supply.
Keywords: angiotensin II type 1a receptor (AT1aR); cardiac dysfunction; high-fat diet; metabolism; mitochondria.