Impact of dietary fat and sucrose consumption on cardiac fibrosis in rhesus monkeys and mice

Abstract

Calorie restriction (CR) improved healthspan in two longitudinal studies in nonhuman primates (NHPs) aimed at investigating the effect of this nutritional intervention on markers of health and survival. However, only the University of Wisconsin (UW) study demonstrated an increase in survival in CR monkeys relative to controls; the National Institute on Aging (NIA) study did not. Using samples from these studies, we investigated the effect of chronic CR on myocardial aging. Age‐associated cardiac changes in NHPs are similar to those of humans, and as such, these samples provide a unique opportunity to further explore cardiac aging and factors that may explain some of the different outcomes between the two NHP studies. We analyzed left ventricle (LV) tissue samples from both studies to assess cardiac fibrosis. Although CR did not reduce cardiac fibrosis or hypertrophy in either study relative to controls, there was a 5.9‐fold increase in fibrosis (p<0.0001) in hearts from UW NHPs compared to NIA, irrespective of CR treatment. Differences in study design have been previously described and one important factor was the composition of the diets that were fed during these three‐decades long studies. UW fed a processed, purified diet with higher levels of sucrose and fat (28% sucrose and 10.6% fat by weight), while the NIA NHPs received a complex natural grain‐based diet containing fish oils (3.9% sucrose, 5% fat by weight). To further explore the intriguing possibility that cardiac fibrosis is affected by dietary composition, we performed rodent experiments using the NHP diets to characterize diet‐associated molecular and functional changes in the heart. Six‐month old male C57BL/6 mice were randomized into one for four diet groups: standard mouse chow, the UW diet, NIA diet, or the NIA diet modified to include increased levels of sucrose and fat equivalent to the UW diet [mNIA]) for six months. Cardiac tissue was then analyzed for fibrosis and RNA‐seq analyses of ventricular tissue. Consistent with the findings from the NHP samples, mice fed UW and mNIA diets had higher cardiac fibrosis. Furthermore, RNA‐seq analyses of hearts showed distinct gene expression signatures among the different diets. At the functional level, expression of cardiac contraction and metabolism genes were upregulated following consumption of the diets with higher sucrose and fat content. These NHP and mouse data suggest that higher dietary fat and sucrose may promote myocardial fibrosis.Support or Funding InformationWork in the Lee laboratory was supported by grants AG047131, AG059129, HL119230 from NIH. The NIA study was supported by the Intramural Research Program of the National Institute on Aging, NIH. The UW study was supported by R01AG040178 (RJC) and was made possible in part by NCRR/ORIP grants P51RR000167/P51OD011106 to the WNPRC.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.