Landscape of heart proteome changes in a diet-induced obesity model

Abstract

Obesity is a pandemic associated with a high incidence of cardiovascular disease; however, the mechanisms are not fully elucidated. Proteomics may provide a more in-depth understanding of the pathophysiological mechanisms and contribute to the identification of potential therapeutic targets. Thus, our study evaluated myocardial protein expression in healthy and obese rats, employing two proteomic approaches. Male Wistar rats were established in two groups (n = 13/group): control diet and Western diet fed for 41 weeks. Obesity was determined by the adipose index, and cardiac function was evaluated in vivo by echocardiogram and in vitro by isolated papillary muscle analysis. Proteomics was based on two-dimensional gel electrophoresis (2-DE) along with mass spectrometry identification, and shotgun proteomics with label-free quantification. The Western diet was efficient in triggering obesity and impaired contractile function in vitro; however, no cardiac dysfunction was observed in vivo. The combination of two proteomic approaches was able to increase the cardiac proteomic map and to identify 82 differentially expressed proteins involved in different biological processes, mainly metabolism. Furthermore, the data also indicated a cardiac alteration in fatty acids transport, antioxidant defence, cytoskeleton, and proteasome complex, which have not previously been associated with obesity. Thus, we define a robust alteration in the myocardial proteome of diet-induced obese rats, even before functional impairment could be detected in vivo by echocardiogram.

Effects of Three-Month Feeding High Fat Diets with Different Fatty Acid Composition on Myocardial Proteome in Mice

“…Additionally, excess dietary linoleic acid (LA) has also been related to increased collagen deposition in the left ventricle in C57BL/6 mice [ 16 ]. Collectively, our data may provide further evidence that high calorie intake triggers metabolic disorders, contributing to cardiac structure and function disorders [ 26 ]. The above-mentioned changes were also accompanied by cardiac protein expression alterations, including those related to cardiomyocyte contractility [ 27 ].…”

“…One of the metabolic consequences of dietary FA overload is increased activity of intracellular enzymes responsible for metabolization of these energetic substrates. Peroxisomal and mitochondrial β-oxidation are the major degradation pathways in fatty acid metabolism [ 26 , 49 ]. A recent study of Sikder et al (2018) showed an increased rate of FA β-oxidation in the hearts of mice subjected to diet-induced obesity [ 50 ].…”

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

“…The results of some previous studies, where non-targeted proteomic methods were applied for the screening of cardiac tissue in animal model of dietary induced obesity, are mostly consistent with our observations. A map of the cardiac proteome in obese rats showed that the proteins involved in regulation of metabolism were predominantly changed [44]. The proteomic machinery responsible for fatty acids uptake and oxidation was upregulated in obese animals without hypertrophied hearts [44].…”

“…A map of the cardiac proteome in obese rats showed that the proteins involved in regulation of metabolism were predominantly changed [44]. The proteomic machinery responsible for fatty acids uptake and oxidation was upregulated in obese animals without hypertrophied hearts [44].…”

Temporal Measures in Cardiac Structure and Function During the Development of Obesity Induced by Different Types of Western Diet in a Rat Model

“…The CD was custom-formulated with the same ingredients as the WDF and WDS except for fructose, sucrose, palm oil, and lard added only in the WDF and WDS, and soybean oil added only in the CD to produce three different diets in fat, protein, and carbohydrate contents (Table 1 and Figure 2). The CD and WDF have been used in our previous study [18]. .…”