<strong>BACKGROUND</strong> This study aimed to investigate the renin-angiotensin system (RAS) and cardiometabolic status in mice fed a long-term high-fat diet (HFD). <strong>MATERIAL AND METHODS</strong> 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). <strong>RESULTS</strong> 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. <strong>CONCLUSIONS</strong> 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.