In:
Medicine & Science in Sports & Exercise, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 1 ( 2021-1), p. 47-57
Abstract:
This study aimed to determine the effect of exercise training on preventing lipotoxic cardiomyopathy and to investigate the role of the 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) and miR-344g-5p in cardiomyocytes. Methods Male C57BL/6 mice were fed a 60% high-fat diet (HFD) for 12 wk then began swimming exercise or remained sedentary for 8 wk. Thereafter, cardiac function was assessed by echocardiography, and heart tissue and plasma were collected for further measurements. The molecular mechanism of exercise was investigated after treating Hmgcs2 siRNA in palmitate-induced neonatal mouse cardiomyocytes. Results HFD induced myocardial hypertrophy and fibrosis and reduced coronary reserve and cardiac function. HMGCS2 levels increased, but junctophilin-2 (JPH2) levels decreased in HFD mice hearts. Such effects were attenuated by swimming exercise. Mechanistically, Hmgcs2 silencing prevented apoptosis and caspase-3 cleavage and elevated the expression of JPH2 in palmitate-stimulated cardiomyocytes. In addition, exercise promoted miR-344g-5p expression in HFD hearts. The overexpression of miR-344g-5p by chemical mimic reduced HMGCS2, apoptosis, and caspase-3 cleavage and elevated JPH2 expression in palmitate-induced cardiomyocytes. Conclusion Our results suggest that exercise limits lipid metabolic disorder, cardiac hypertrophy, and fibrosis and aids in the prevention of lipotoxic cardiomyopathy. Exercise-mediated cardioprotection by upregulating miR-344g-5p, which targets Hmgcs2 mRNA, prohibits HMGCS2 upregulation and thus lipotoxicity.
Type of Medium:
Online Resource
ISSN:
1530-0315
,
0195-9131
DOI:
10.1249/MSS.0000000000002453
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2021
detail.hit.zdb_id:
2031167-9
SSG:
31
Permalink