Short‐term Western Diet Induces Cardiometabolic Syndrome in Female Rats is Associated with Increased Cardiovascular Protein Lysine Acetylation.

Abstract

The western diet (WD), which is rich in fat, carbohydrates, and refined sugars, is a major contributor to the global epidemic of metabolic syndrome in our modern society. Despite the well‐documented cardioprotection exhibited by the pre‐menopausal female population, studies have indicated that certain stressors may abolish this cardiovascular protection. Studies on the impact of the WD on the cardiometabolic profile of female cohorts remains limited. Lysine acetylation, a reversible posttranslational modification of histone and non‐histone proteins, has been closely associated with metabolic disorders. Based on these factors, we hypothesized that short‐term exposure to the WD alters cardiometabolic parameters in premenopausal rats and alters levels of lysine acetylation in the cardiovascular tissues. Adult female Wistar rats were randomized in two groups: Control Group (n=8) was assigned a regular chow diet and WD Group (n=12) received WD (40% fat, 43% carbohydrates, and 17% protein) for 17 weeks. Results showed that WD group exhibited increased body weight (376 ± 49 vs 305 ± 41g, p<0.05), periabdominal fat content (30 ±11 vs 11 ±2g, p<0.01), % body fat (8.1 ±1.0 vs 3.6 ±0.4%, p<0.01), and serum triglyceride levels (56 ± 13 vs 25 ± 4 mg/dl, p<0.01) compared to controls. Although the WD group exhibited significant increases in glucose intolerance (AUC: 17068.5 ± 730 vs. 13787.67± 814 a.u, p<0.01) and insulin resistance (HOMA‐IR: 5.75 ± 0.9 vs. 3.25 ± 0.62 control, p<0.05), no differences in fasting blood glucose and hemoglobin A1C were found. Using direct arterial blood pressure measurements via carotid artery catheterization, we observed increased systolic blood pressure (146.19 ±9.4 vs 126.22 ± 9.8 mmHg controls, p<0.001), which is contradictory with previous studies. Our vascular reactivity studies revealed that short‐term WD markedly impaired endothelial‐dependent relaxation. Additionally, using DHE staining we found that aortas from the WD group exhibited augmented levels of oxidative stress (3.1‐fold increase vs. control, p<0.001). Strikingly, levels of global lysine acetylation were markedly elevated in the aortas (2.2‐fold increase vs. control, p<0.01) and heart (1.4‐fold increase vs. control, p<0.05) of WD group. Levels of acetyltransferase PCAF were significantly upregulated in the aortas (2.2‐fold increase vs. control, p<0.05). Interestingly, PCAF and deacetylase HDAC9 expression was diminished in hearts from WD group (30% reduction vs. control, p<0.05) and (85% reduction vs. control, p<0.05), respectively. Besides these cardiovascular alterations, the WD also led to the development of non‐alcoholic fatty liver disease (NAFLD) and robust increases in hepatic global lysine acetylation (3.0‐fold increase vs. control, p<0.001). Taken together, our results demonstrated that, even under short‐term exposure, the WD negatively affects the metabolic and cardiovascular parameters of female rats and it is associated with elevated levels of global lysine acetylation in cardiometabolic tissues. This study will be further conducted to identify the specific proteins acetylated in blood vessels and heart from female population under WD regimes.Support or Funding InformationIn‐house Grant NYIT to MACSThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.