Does a High‐Fat Diet Mimic Biological Aging in Mice? A Preliminary Study

Abstract

Age and obesity are risk factors for many chronic diseases, which are linked to inflammation and oxidative stress, and is thought to alter telomere function. Telomeres are the endcaps of eukaryotic chromosomes that maintain chromosomal structural integrity protecting genetic information. Telomeres are regulated and protected by the shelterin complex, made up of Telomere‐repeat binding factor 1 (TRF1) and 2 (TRF2), protection of telomeres 1 (POT1a and b) as well as the enzyme telomerase that can elongate telomeres. However, to date, the effect of a high‐fat diet and age on the shelterin complex of telomeres in adipose tissue has not been examined. Thus, the present study investigated the effects of a high‐fat diet and aging on C57Bl6J (N=15) mice adipose tissue mRNA expression of genes involved in the regulation of telomeres. Young mice were randomly assigned to be fed either a high‐fat (YG+HF; n=5; 60% kcal from fat) or a low fat diet (YG+LF; n=4; 10% kcal from fat) for three months. A subset of mice were fed a low fat diet (AGED; n=6; 10% kcal from fat) and aged until 16 months.RESULTSBody weight and epididymal white adipose tissue weight (EWAT) increased with age or a high‐fat diet. TRF1 mRNA expression was reduced by age and a high‐fat diet, whereas age alone reduced TRF2. mTERT, the gene that codes for the catalytic subunit of the enzyme telomerase, was significantly higher in the YG+HF than the YG+LF and AGED mice (p=0.001). Body weight was significantly correlated with TRF1 and TRF2 mRNA expression (p=0.01), whereas mTERT expression was significantly correlated to EWAT weight (p=0.008). There were no significant differences between groups for mRNA expression of POT1A (p=0.928) and POT1B (p=0.930), respectively. To understand potential impacts of alterations to shelterin complex proteins on phenotype we probed for tumor necrosis factor α (TNFα) and monocyte chemoattractant protein 1 (MCP1), though unexpectedly, mRNA expression in adipose tissue were significantly elevated in the YG+LF group compared to the YG+HF and aged groups for TNFα (p=0.001) and MCP1 (p=0.000), respectively. We also assessed gene expression of the tumor suppressor protein p53, which is involved in the DNA damage response. There was no significant difference between groups for p53 mRNA expression (p=0.199). A high‐fat diet, increased the expression of mTERT, the catalytic subunit of the enzyme telomerase, but decreased TRF1, whereas age decreased mTERT, TRF1, and TRF2. POT1a, POT1b, p53 were not different. Together, these findings suggest diet and age impact expression of the shelterin complex, and perhaps telomere function in adipose tissue which might be associated with the development of chronic disease associated with obesity or aging, but further work is needed.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.