Proteomic and Structural Manifestations of Cardiomyopathy in Rat Models of Obesity and Weight Loss

Front Endocrinol (Lausanne). 2021 Feb 24:12:568197. doi: 10.3389/fendo.2021.568197. eCollection 2021.

Abstract

Obesity cardiomyopathy increases the risk of heart failure and death. Obesity is curable, leading to the restoration of the heart phenotype, but it is not clear if there are any after-effects of obesity present after weight loss. We characterize the proteomic landscape of obesity cardiomyopathy with an evaluation of whether the cardiac phenotype is still shaped after weight loss. Cardiomyopathy was validated by cardiac hypertrophy, fibrosis, oversized myocytes, and mTOR upregulation in a rat model of cafeteria diet-induced developmental obesity. By global proteomic techniques (LC-MS/MS) a plethora of molecular changes was observed in the heart and circulation of obese animals, suggesting abnormal utilization of metabolic substrates. This was confirmed by increased levels of cardiac ACSL-1, a key enzyme for fatty acid degradation and decreased GLUT-1, a glucose transporter in obese rats. Calorie restriction and weight loss led to the normalization of the heart's size, but fibrosis was still excessive. The proteomic compositions of cardiac tissue and plasma were different after weight loss as compared to control. In addition to morphological consequences, obesity cardiomyopathy involves many proteomic changes. Weight loss provides for a partial repair of the heart's architecture, but the trace of fibrotic deposition and proteomic alterations may occur.

Keywords: cafeteria diet; caloric restriction; cardiac fibrosis; developmental obesity; heart proteomics; obesity cardiomyopathy; plasma proteomics; weight loss.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caloric Restriction
  • Cardiomegaly / metabolism
  • Cardiomegaly / pathology
  • Cardiomyopathies* / etiology
  • Cardiomyopathies* / metabolism
  • Cardiomyopathies* / pathology
  • Disease Models, Animal
  • Male
  • Myocardium / metabolism
  • Myocardium / pathology
  • Myocardium / ultrastructure
  • Obesity* / complications
  • Obesity* / diet therapy
  • Obesity* / metabolism
  • Obesity* / pathology
  • Proteome / analysis
  • Proteome / metabolism
  • Proteomics
  • Rats
  • Rats, Long-Evans
  • Weight Loss / physiology*

Substances

  • Proteome