ABC | Volume 112, Nº5, May 2019

Original Article Effting et al RE Effects: heart and obesity Arq Bras Cardiol. 2019; 112(5):545-552 that can be mediated by RE is the Nuclear Factor Erythroid 2 (NRF2) translocation to the nucleus and expression of several antioxidant enzymes such as NADH: quinone oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO1). which help to detoxify the biological system and contribute to the reduction of oxidative stress. 35 Merry and Ristow (2016) 36 suggest that exercise may stimulate NRF2 translocation to functionally regulate mitochondrial biogenesis of skeletal muscle and the expression of antioxidants defense genes. Although these results are obtained from aerobic training and in skeletal muscle, it is believed that such effects may also occur via resistance training, as resistance training activates the Adenosine Monophosphate-Activated Protein Kinase (AMPK) 37 , which enhances the phosphorylation of NRF2 in the cell and increases the level of phosphorylated NRF2 in the nucleus. 38 The increased production of oxidants in the myocardium can be mediated by a possible inflammatory response induced by obesity/HFD with the secretion of different mediators. In this context, TNF- α is a mediator sensitive to the HFD model that shows a wide range of pro-inflammatory actions. Our results showed a significant increase in TNF- α levels in DIO animals with a consequent reduction after resistance training. Increased levels of TNF- α in the myocardium induced by a HFD have also been observed in previous studies. 3,28 The effects of exercise may be related to the fact that aerobic and resistance exercises promote increased secretion of anti‑inflammatory cytokines and regulate TNF- α levels. 30,31 During the exercise, the muscles release myosins, which are involved in tissue growth, repair and anti‑inflammatory responses. 39 IL-6 is the primary myosin released in response to exercise and increases IL-10 and decreases TNF- α levels. 40 IL-10 reduces cardiac dysfunction by decreasing cardiac fibrosis. 39 In this scenario, HFD‑induced obesity decreases IL-10 protein levels, but physical training significantly increases the IL-10 levels in cardiac tissues. 3 According to data from previous studies, the control of TNF- α secretion in the myocardium by RE is considered an important factor in the cardioprotection mechanisms related to oxidative stress. Conclusion Our results showed an important effect of RE on the control/ stabilization of body weight even without food intake control. It was also demonstrated that there is a redox alteration in the cardiac tissue with an obesity model, but it does not seem to be mediated mainly by the classic antioxidant production and control of hydrogen peroxide, but rather by other reactive species. However, RE was able to reverse lipid damage and the production of reactive species, even with the consumption of a HFD, as well as positively modulate one of the main cytokines responsible for the activation of the inflammatory process. Therefore, RE can be a great ally in the health process regarding the therapeutic approach to obesity. Some limitations found in these studies were the data related to the quantification of serum insulin to better confirm insulin resistance, and the evaluation of other molecules that can alter the cell redox balance. These tests were not performed for technical reasons. Finally, other studies should be performed aiming to better explain how RE promotes these effects, particularly in the regulation of reactive species such as hydroxyl, peroxyl, nitric oxide and peroxide nitrite, as well as other inflammatory and anti-inflammatory parameters in cardiac tissue. Author contributions Conception and design of the research: Ceddia RB, Pinho RA; Acquisition of data: Brescianini SMS, Fernandes BB, Fidelis GSP, da Silva PRL, Nesi RT; Analysis and interpretation of the data: Effting PS, Brescianini SMS, Silveira PCL, Nesi RT, Pinho RA; Statistical analysis: Effting PS, Silveira PCL, Pinho RA; Obtaining financing: Pinho RA; Writing of the manuscript: Effting PS, Pinho RA; Critical revision of the manuscript for intellectual content: Ceddia RB, Pinho RA. Potential Conflict of Interest No potential conflict of interest relevant to this article was reported. Sources of Funding This study was funded by CNPq and Capes. Study Association This article is part of the thesis of Doctoral submitted by Pauline Souza Effting, from Universidade do Extremo Sul Catarinense. Ethics approval and consent to participate This study was approved by the Ethics Committee on Animal Experiments of the Universidade do Extremo Sul Catarinense under the protocol number 067/2014-2. 1. WHO - World Healt Organization. Global Health Observatory (GHO) data. Overweight and obesity [Internet]. Copenhagen:WHO; 2018 [citado 30 jul. 2018. Disponível em: http://www.who.int/gho/ncd/risk_factors/ overweight_obesity/obesity_adults/en/. 2. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, Esquivel-Soto J, Morales-González Á, Esquivel-Chirino C, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011;12(5):3117-32. 3. Kesherwani V, Chavali V, Hackfort BT, Tyagi SC, Mishra PK. Exercise ameliorates high fat diet induced cardiac dysfunction by increasing interleukin 10. Front Physiol. 2015 Apr 22;6:124. 4. Sakurai T, Izawa T, Kizaki T, Ogasawara J, Shirato K, Imaizumi K, et al. Exercise training decreases expression of inflammation-related adipokines through reduction of oxidative stress in rat white adipose tissue. Biochem Biophys Res Commun. 2009;379(2):605-9. References 550