Obesity‐Mediated Regulation of the Cardiac Acetylome

Abstract

Lysine residues undergo diverse and reversible post‐translational modifications that include acetylation, ubiquitylation and methylation. Lysine acetylation has traditionally been studied in the regulation of gene expression, where acetylation of histone tails alters electrostatic interactions of nucleosomal DNA. However, recent proteomic studies have identified ~4,000 proteins that can be acetylated on ~10,000 lysine residues, suggesting a more complex role for the acetylome in biological function. In the heart, treatment with histone deacetylase (HDAC) inhibitors and thus increases in lysine acetylation have been shown to be cardioprotective. Here we examined the impact of obesity on the regulation of lysine acetylation. In this study, male and female c57BL/6J mice fed a high fat diet (60% kcal from fat) had a significant increase in body weight, heart weight and left ventricle weight compared to mice fed a control diet (10% kcal from fat). Of interest, immunoblot analysis demonstrated that lysine acetylation of the left ventricle was markedly altered in both male and female mice in response to diet‐induced obesity. Moreover, these phenomena appeared to be cardiac tissue specific as no differences in lysine acetylation were observed in skeletal muscle, liver or white adipose tissue in response to obesity. As such, we recently performed isobaric tagging and mass spectral analysis to identify and quantitatively analyze changes in protein abundances as well as lysine acetylation in response to obesity. We postulate that our investigations will demonstrate, with statistical significance, the impact of obesity on regulation of the cardiac acetylome and uncover biological pathways regulated by protein acetylation potentially involved in cardiac pathology.Support or Funding InformationThe project described was supported by a grant from the National Institute of General Medical Sciences (GM103440). This work is supported by the USDA National Institute of Food and Agriculture (Hatch‐NEV00727).