Sodium Selenate Ameliorates Cardiac Injury Developed from High-Fat Diet in Mice through Regulation of Autophagy Activity

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.

Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

“…The molecular mechanisms of autophagy regulation remain unclear, an in-depth study of mTOR-4EBP1 pathway might thus contribute to provide an exciting therapeutic strategy for DCM [24][25][26]. Our data indicated that rapamycin down-regulated the mTOR-4EBP1 signaling pathway in DCM mice.…”

Voluntary activity reverses spermidine-induced myocardial fibrosis and lipid accumulation in the obese male mouse

“…This suggests that the overproportional lipid accumulation is no direct effect of spermidine but is rather based on an interaction between the cellular disturbances induced by HFD and spermidine. For example, cell culture and mouse experiments indicate that high lipid burden leads to increased autophagosome generation but less autophagosome degradation (Zhang et al 2019 ). Additional interference with the dysregulated autophagic machinery by exogenous spermidine might therefore increase the imbalance and have adverse effects.…”

Up-regulating autophagy by targeting the mTOR-4EBP1 pathway: a possible mechanism for improving cardiac function in mice with experimental dilated cardiomyopathy

“…The molecular mechanisms of autophagy regulation remain unclear, an in-depth study of mTOR-4EBP1 pathway might thus contribute to provide an exciting therapeutic strategy for DCM [24][25][26].…”