Western Diet‐Induced Metabolic Memory and Persistent Vascular Dysfunction in Female Rats

Abstract

Metabolic memory is a phenomenon by which the body remembers previous exposure to metabolic stressors, such as hyperglycemia. Consumption of a western diet (WD) is a major part of modern life contributing to the epidemic of Metabolic Syndrome (MS), a significant risk factor for cardiovascular disease. Recent studies from our laboratory have characterized a model of WD induced MS in female rats. If not treated early, MS often progresses to Type II Diabetes Mellitus (T2DM). Adopting a healthier diet prior to onset of T2DM may be sufficient to reverse the constellation of metabolic symptoms associated with MS including hyperglycemia, hypertriglyceridemia, and increased body fat around the waist. However, it remains unclear if this diet reversal overcomes metabolic memory and cardiovascular dysfunction associated with MS. We hypothesize that cardiovascular dysfunction will persist despite diet reversal due to the development of metabolic memory. Eight‐week old female Wistar rats were fed a WD (21% fat, 50% carbohydrate (34% sucrose), 20% protein) for 17 weeks (WD group) to induce MS. Then, the rats were subjected to diet reversal for 8 weeks (rWD group). The control group received a regular chow diet (5% fat, 48.7% carbohydrate (3.2% sucrose), 24.1% protein). Metabolic (body weight, triglycerides, free fatty acids, glucose tolerance) and cardiovascular (blood pressure and vascular reactivity) parameters were assessed. WD group showed increased body weight, triglyceride levels, and systolic blood pressure characterizing MS. Moreover, fatty liver was observed in the WD group. As expected, rWD group exhibited improvement of all metabolic parameters and reversal of fatty liver (Figure 1). WD group showed marked increases in systolic blood pressure, measured via right carotid catheterization. Using wire myography, cumulative concentration curves were performed for acetylcholine and sodium nitroprusside. We found a significant impairment of endothelium dependent and independent vasorelaxation, respectively. Surprisingly, the rWD group did not decrease blood pressure (Figure 2) or improve impaired vasorelaxation. These results indicate that WD causes long‐lasting cardiovascular complications that are not alleviated by diet reversal. Our findings show for the first time that exposure to a WD can lead to metabolic memory in the cardiovascular system. We will extend our studies to examine potential mechanisms of metabolic memory leading to persistent cardiovascular dysfunction.Support or Funding InformationIn‐house Grant NYITThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.