Abstract
Obesity is often accompanied by dyslipidemia, high blood glucose, hypertension, atherosclerosis, and myocardial dysfunction. Selenate is a vital antioxidant in the cardiovascular system. The beneficial effects of selenate on obesity-associated cardiac dysfunction and potential molecular mechanism were identified in both H9C2 cells and C57BL/6J mice hearts. The cardiac histological preformation in C57BL/6J mice were evaluated by cross-sectional area (CSA) of cardiomyocytes and percent area of fibrosis in the left ventricles. The cardiac autophagy flux in H9C2 cells and C57BL/6J mice hearts was analyzed by Western blots and the number of autophagosomes and autolysosome in H9C2 cells. In the present study, we found that lipid overload caused increases in serum lipid, CSA, and percent area of fibrosis. We further found that lipid-induced accumulation of autophagosomes was due to depressed autophagy degradation, which was not restored in the pretreatment with 3-methyladenine and chloroquine, whereas, it was improved by rapamycin. Moreover, we demonstrated that increased levels of serum lipid, CSA, percent area of fibrosis and mRNA expression related to cardiomyocytes hypertrophy and fibrosis were significantly reduced after selenate treatments of mice. We also found selenate treatment significantly down-regulated activity of the Akt pathway, which was activated in response to lipid-overload. Furthermore, selenate dramatically improved cardiac autophagic degradation which was suppressed after exposure to lipid-overload in both H9C2 cells and C57BL/6J mice hearts. Taken together, selenate offers therapeutic intervention in lipid-related metabolic disorders, and protection against cardiac remodeling, likely through regulation of the activity of autophagic degradation and Akt pathway.