Exercise prevents fatal stress-induced myocardial injury in obese mice

Abstract

IntroductionThis study aimed to explore whether aerobic exercise (AE) can prevent fatal stress-induced myocardial injury.MethodsThirty C57BL/6J mice were divided into either a normal diet, high-fat diet, or high-fat diet plus AE (n=10 per group). The AE protocol consisted of eight weeks of swimming. At the end of the diet and AE interventions, the mice were stimulated with fatal stress caused by exhaustive exercise (forced weight-loaded swimming until exhaustion), after which cardiac function was evaluated using echocardiography, myocardial ultrastructure was examined using transmission electron microscopy, and myocardial apoptosis was assessed using western blotting and TUNEL. Mitophagy, mitochondrial biogenesis and dynamics, and activation of the macrophage migration inhibitor factor (MIF)/AMP-activated protein kinase (AMPK) pathway were evaluated using quantitative PCR and western blotting. Obesity phenotypes were assessed once per week.ResultsAE reversed high-fat diet-induced obesity as evidenced by reductions in body weight and visceral fat compared to obese mice without AE. Obesity exacerbated fatal stress-induced myocardial damage, as demonstrated by impaired left ventricular ejection fraction and myocardial structure. The apoptotic rate was also elevated upon fatal stress, and AE ameliorated this damage. Obesity suppressed mitophagy, mitochondrial fission and fusion, and mitochondrial biogenesis, and these effects were accompanied by suppression of the MIF/AMPK pathway in the myocardium of mice subjected to fatal stress. AE alleviated or reversed these effects.ConclusionThis study provides evidence that AE ameliorated fatal stress-induced myocardial injury in obese mice. The cardioprotective effect of AE in obese mice might be attributed to improved mitochondrial quality.

The role of mitophagy in metabolic diseases and its exercise intervention

“…These result in impaired cardiac mitophagy, deficient mitochondrial biogenesis, and impaired mitochondrial fission/fusion. Eight-week swimming exercise pre-conditioning attenuates one-time exhaustion exercise-induced MQC deficits in the heart of obese mice, increases PINK1, SIRT1, PGC-1α, Mfn1, and Drp1 protein expression, decreases p62 and Cyt-c protein levels, promotes mitophagy, mitochondrial biogenesis, and mitochondrial fission/fusion homeostasis, which in turn downregulates Bax protein expression, increases Bcl-2 and Bcl-2/BAX levels, and inhibits cardiac apoptosis in obese mice ( Dun et al, 2023 ). After combined intervention with low-intensity continuous swimming exercise, high-intensity continuous swimming exercise, and high-intensity interval swimming exercise in male Swiss mice, the expression of PGC-1α mRNA in the gastrocnemius muscle of the exercise group increases at 6, 12, and 24 h post-exercise compared with that in the sedentary group.…”

“…In addition, swimming significantly increased the LC3-I to LC3-II conversion rate in the heart of obese mice induced by a single session of exhaustive exercise, upregulated the protein expression of PINK1, SIRT1, PGC-1α, Mfn1, and Drp1, decreased the levels of p62 and Cyt-c, promoted mitophagy, mitochondrial biogenesis, and mitochondrial fission/fusion homeostasis. Then, it also downregulated the levels of BAX protein, increased Bcl-2 and Bcl-2/BAX levels, inhibited cardiac apoptosis, and attenuated single bout of exhaustive exercise-induced cardiac functional impairment ( Dun et al, 2023 ). Aerobic exercise for 8 weeks significantly increased the protein levels of Opa1 and Mfn1, decreased the protein levels of Fis1, Pink, Parkin, and LC3 II, decreased mitochondrial H 2 O 2 release and mitochondrial O 2 respiration, and increased mitochondrial Ca2 + retention in the hearts of aging rats.…”