Dysregulation of the Renin-Angiotensin System and Cardiometabolic Status in Mice Fed a Long-Term High-Fat Diet.

BACKGROUND This study aimed to investigate the renin-angiotensin system (RAS) and cardiometabolic status in mice fed a long-term high-fat diet (HFD). MATERIAL AND METHODS C57BL/6J mice were randomly assigned to the control group on a normal diet (ND) (n=15) and the HFD group (n=15). Serum biomarkers were measured, including total cholesterol (TC), triglyceride (TG), insulin, glycated hemoglobin (HbA1c), brain natriuretic peptide (BNP), renin, angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), Ang-II type 1 receptor (AT₁R), and aldosterone. Cardiac histology was measured by the cross-sectional area (CSA) of cardiomyocytes and collagen deposition. Levels of myocardial intercalated disc (ICD) proteins and mRNA were analyzed by Western blot and real-time quantitative polymerase chain reaction (RT-qPCR), respectively. The localization of ICD proteins was evaluated by immunohistochemistry (IHC). RESULTS Compared with ND, HFD resulted in increased blood glucose, body weight, TC, TG, HbA1c, insulin, and BNP and levels of serum ACE, Ang-II, aldosterone, AT₁R, cardiomyocyte CSA, and interstitial collagen in the myocardium compared. Also, HFD significantly down-regulated connexin-43, and upregulated ß-catenin, N-cadherin, and plakoglobin in the hearts of HFD mice compared with ND mice. However, the deposition of ICD proteins was not changed in the hearts of HFD mice compared with ND mice. CONCLUSIONS Long-term HFD in mice resulted in left ventricular hypertrophy, interstitial fibrosis, dysregulation of RAS, and abnormal expression of ICD proteins compared with ND mice, but did not affect the distribution of cardiomyocyte ICD proteins. Long-term HFD resulted in cardiac remodeling and altered expression of ICD proteins through RAS activation.