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| Author(s): |
Danielle Fernandes Vileigas
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | Botucatu. 2019-04-08. |
| Institution: | Universidade Estadual Paulista (Unesp). Faculdade de Medicina. Botucatu |
| Defense date: | 2019-02-26 |
| Advisor: | Antonio Carlos Cicogna |
| Abstract | |
Obesity is a complex metabolic disease considered a global pandemic and associated with high incidence of cardiovascular disease. The excess of adipose tissue may promotes maladaptation that result in alterations in structure and function of the heart; however, the mechanisms are not fully elucidated. Proteomics may provide a deeper understanding into the pathophysiological process and contribute to the identification of new potential therapeutic targets. Thus, the aim of this was evaluate the myocardial protein expression in healthy and obese rats, employing two proteomic approaches to better comprehend the network of mechanisms inherent to cardiac dysfunction in obesity. Male Wistar rats were distributed into two groups: control (C, n=13; standard diet) and obese (Ob, n=13; Western diet) fed for 41 weeks. The obesity was determined by adipose index. Cardiac function was evaluated by echocardiogram and isolated papillary muscle analysis. The proteomics was based on two-dimensional gel electrophoresis (2-DE) along with mass spectrometry identification (LC-MS/MS) and nano-liquid chromatography with tandem mass spectrometry (nanoLC-MS/MS) followed by label-free quantification. Obese rats showed increased adiposity index and systolic and diastolic cardiac dysfunction. A total of 82 myocardial proteins was identified as differentially expressed between C and Ob groups using two proteomic strategies, being 43 up- and 39 down-regulated by obesity. These proteins are involved in important biological processes including mitochondrial and peroxisomal fatty acid beta-oxidation, intracellular lipid homeostasis, metabolic process of glucose and amino acid, tricarboxylic acid cycle, oxidative phosphorylation, antioxidant defenses, contractile function and regulation of calcium transient. Interestingly, the proteomic data indicated high and low expression of several cytoskeletal and proteasome complex proteins, respectively, in obese rat myocardium, which have not previously been associated with cardiac dysfunction in obesity. Furthermore, the combination of both 4 proteomic techniques may be relevant to increase the cardiac proteomic map. In conclusion, the proteomic findings revealed diverse alterations in myocardial proteome from obese rats, enabling novel insights concerning the mechanisms involved in cardiac functional impairment due to obesity and possible new therapeutic targets. (AU) | |
| FAPESP's process: | 14/22152-0 - Myocardial proteome of obese rats by Western diet with cardiac dysfunction |
| Grantee: | Danielle Fernandes Vileigas |
| Support Opportunities: | Scholarships in Brazil - Doctorate |