Proteomic and structural heart changes in obese rats are incompletely restored after weight loss

Abstract

Background As a systemic disorder, obesity strongly affects the cardiovascular system, inducing cardiac overgrowth, which increases the risk of heart failure and death. Moreover, obesity is potentially curable, leading to the restoration of the heart phenotype, but it is not clear if all of the after-effects are reversed after weight loss. of the heart phenotype, but it is not clear if all of the after-effects are reversed after weight loss. Here we describe the proteomic and morphologic phenotype of the heart in a rat model of developmental obesity with an evaluation of whether the observed effects are persistent in spite of weight loss. Methods Developmental obesity with hyperlipidemia and insulin resistance was induced in young rats by exposure to a Western diet composed of human snacks. An histologic evaluation of the heart was performed to measure the size of the cardiomyocytes and amount of connective tissue discriminating the phenotype of obesity cardiomyopathy. The cardiac tissue and plasma were analyzed by global proteomic profiling. Based on these data, we targeted proteins for evaluation with the western blot. The histological and proteomic measurements were performed after weight loss to validate which features of obesity cardiomyopathy were persistent. Results Obesity cardiomyopathy was determined as cardiac hypertrophy associated with fibrosis, oversized myocytes, and mTOR upregulation. A plethora of molecular changes were observed, suggesting an effect on the utilization of metabolic substrates in the hearts of obese animals. This was confirmed by increased levels of ACSL-1, a key enzyme for fatty acid degradation and decreased GLUT-1, a glucose transporter. Immunological processes and lipid metabolism were also affected in the cardiac tissue and plasma. Weight loss led to the normalization of the heart’s size, but some after-effects of obesity such as connective tissue abundance and abnormal proteomic composition were still persistent. Conclusion In addition to morphological consequences, obesity cardiomyopathy involves many proteomic changes. Obesity treatment and weight loss provides for a partial repair of the heart’s architecture, but cardiac fibrosis and some proteomic alterations persist.

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

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