Diet-induced leukocyte telomere shortening in a baboon model for early stage atherosclerosis

Genesio M Karere,Angelica M Riojas,John L Vandeberg,Michael C Mahaney,Deborah E Newman,Clint Christensen,Shifra Birnbaum,Laura Cox

doi:10.1038/s41598-019-55348-8

Abstract

Reported associations between leukocyte telomere length (LTL) attrition, diet and cardiovascular disease (CVD) are inconsistent. This study explores effects of prolonged exposure to a high cholesterol high fat (HCHF) diet on LTL in a baboon model of atherosclerosis. We measured LTL by qPCR in pedigreed baboons fed a chow (n = 105) or HCHF (n = 106) diet for 2 years, tested for effects of diet on LTL, and association between CVD risk factors and atherosclerotic lesions with LTL. Though not different at baseline, after 2 years median LTL is shorter in HCHF fed baboons (P < 0.0001). Diet predicts sex- and age-adjusted LTL and LTL attrition (P = 0.0009 and 0.0156, respectively). Serum concentrations of CVD biomarkers are associated with LTL at the 2-year endpoint and LTL accounts approximately 6% of the variance in aortic lesions (P = 0.04). Although heritable at baseline (h2 = 0.27, P = 0.027) and after 2 years (h2 = 0.46, P = 0.0038), baseline LTL does not predict lesion extent after 2 years. Atherogenic diet influences LTL, and LTL is a potential biomarker for early atherosclerosis. Prolonged exposure to an atherogenic diet decreases LTL and increases LTL attrition, and shortened LTL is associated with early-stage atherosclerosis in pedigreed baboons.

Highlights

We have shown that a diet previously demonstrated to be atherogenic in captive baboons from a pedigreed breeding colony affects LTL and that the effects of diet are in addition to those of aging
We have shown that diet-induced shorter LTL is negatively associated with extent of vascular lesion development in early-stage atherosclerosis
Both observations have been made in the same individuals, in the course of the same study

Summary

Methods

The study described in this paper utilizes data from 2 groups of baboons distinguished by diet. Baboons in the control group were fed a baseline diet (chow), low in cholesterol (0.021 mg/kcal) and fat (10% kcal), throughout the study. Baboons in the experimental diet group were fed the chow diet prior to beginning a 2-year dietary challenge during which they were fed a diet high in cholesterol (approximately 1.865 mg/kcal) and fat (40% kcal; HCHF). Summaries of raw data are presented by cohort, time-point, and sex as means, medians, standard deviations, and ranges. As some departures from univariate normality (e.g., skew) affect the mean more than the median, we instead use the latter as the measure of central tendency in our initial comparisons of raw data. We employ a Wilcoxon-Mann-Whitney U test of medians that implements an exact permutation approach which is robust to the presence of outliers[25]

Results

Discussion

Conclusion