Key result
Endurance exercise ameliorated high-fat/high-fructose diet-induced cardiac disruption, reversed myocyte premature senescence, and restored autophagy flux in female mice.
Why the study?
Whether endurance exercise-induced cardioprotection against metabolic diseases is associated with mitigating senescence in females remains unknown.
Does endurance exercise mitigate metabolic disorder-induced cardiac disruption in a female mouse model of obesity/type 2 diabetes?
Does endurance exercise mitigate metabolic disorder-induced cardiac disruption in a female mouse model of obesity/type 2 diabetes?
Endurance exercise mitigates metabolic disorder-induced cardiac disruption in female mice by reducing cellular senescence and restoring autophagy.
Should not change practice in metabolic cardiomyopathy; leaves open translation of exercise effects on cardiac senescence from female mice.
INTRODUCTION: Metabolic disorder promotes premature senescence and poses more severe cardiac dysfunction in females than males. Although endurance exercise (EXE) has been known to confer cardioprotection against metabolic diseases, whether EXE-induced cardioprotection is associated with mitigating senescence in females remains unknown. Thus, the aim of the present study was to examine metabolic disorder-induced cardiac anomalies (cellular senescence, metabolic signaling, and autophagy) using a mouse model of obese/type 2 diabetes induced by a high-fat/high-fructose (HFD/HF) diet. METHODS: Female C57BL/6 mice (10 wk old) were assigned to three groups ( n = 11/group): normal diet group (CON), HFD/HF group, and HFD/HF diet + endurance exercise (HFD/HF + EXE) group. Upon confirmation of hyperglycemia and overweight after 12 wk of HFD/HF diet, mice assigned to HFD/HF + EXE group started treadmill running exercise (60 min·d -1 , 5 d·wk -1 for 12 wk), with HFD/HF diet continued. RESULTS: EXE ameliorated HFD/HF-induced body weight gain and hyperglycemia, improved insulin signaling and glucose transporter 4 (GLUT4) levels, and counteracted cardiac disruption. EXE reversed HFD/HF-induced myocyte premature senescence (e.g., prevention of p53, p21, p16, and lipofuscin accumulation), resulting in suppression of a senescence-associated secretory phenotype such as inflammation (tumor necrosis factor α and interleukin-1β) and oxidative stress (protein carbonylation). Moreover, EXE restored HFD/HF-induced autophagy flux deficiency, evidenced by increased LC3-II concomitant with p62 reduction and restoration of lysosome function-related proteins (LAMP2, CATHEPSIN L, TFEB, and SIRT1). More importantly, EXE retrieved HFD/HF-induced apoptosis arrest (e.g., increased cleaved CASPASE3, PARP, and TUNEL-positive cells). CONCLUSIONS: Our study demonstrated that EXE-induced antisenescence phenotypes, autophagy restoration, and promotion of propitiatory cell removal by apoptosis play a crucial role in cardiac protection against metabolic distress-induced cardiac disruption.
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Ko et al. (2022) studied Metabolic disorder-induced cardiac anomalies (n=33). Endurance exercise vs. HFD/HF diet without exercise was evaluated on Cardiac disruption, cellular senescence, metabolic signaling, and autophagy. Endurance exercise ameliorated high-fat/high-fructose diet-induced cardiac disruption, reversed myocyte premature senescence, and restored autophagy flux in female mice.
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