ObjectiveMitochondria‐associated membranes (MAMs) serve pivotal functions in hepatic insulin resistance (IR). Our aim was to explore the potential role of MAMs in mitigating hepatic IR through exercise and to compare the effects of different intensities of exercise on hepatic MAMs formation in high‐fat diet (HFD) mice.MethodsMale C57BL/6J mice were fed an HFD and randomly assigned to undergo supervised high‐intensity interval training (HIIT) or moderate‐intensity continuous training (MICT). IR was evaluated using the serum triglyceride/high‐density lipoprotein cholesterol ratio (TG/HDL‐C), glucose tolerance test (GTT), and insulin tolerance test (ITT). Hepatic steatosis was observed using hematoxylin–eosin (H&E) and oil red O staining. The phosphatidylinositol 3‐kinase/protein kinase B/glycogen synthase kinase 3 beta (PI3K‐AKT‐GSK3β) signaling pathway was assessed to determine hepatic IR. MAMs were evaluated through immunofluorescence (colocalization of voltage‐dependent anion‐selective channel 1 [VDAC1] and inositol 1,4,5‐triphosphate receptor [IP3R]).ResultsAfter 8 weeks on an HFD, there was notable inhibition of the hepatic PI3K/Akt/GSK3β signaling pathway, accompanied by a marked reduction in hepatic IP3R‐VDAC1 colocalization levels. Both 8‐week HIIT and MICT significantly enhanced the hepatic PI3K/Akt/GSK3β signaling and colocalization levels of IP3R‐VDAC1 in HFD mice, with MICT exhibiting a stronger effect on hepatic MAMs formation. Furthermore, the colocalization of hepatic IP3R‐VDAC1 positively correlated with the expression levels of phosphorylation of protein kinase B (p‐AKT) and phosphorylation of glycogen synthase kinase 3 beta (p‐GSK3β), while displaying a negative correlation with serum triglyceride/high‐density lipoprotein cholesterol levels.ConclusionThe reduction in hepatic MAMs formation induced by HFD correlates with the development of hepatic IR. Both HIIT and MICT effectively bolster hepatic MAMs formation in HFD mice, with MICT demonstrating superior efficacy. Thus, MAMs might wield a pivotal role in exercise‐induced alleviation of hepatic IR.image

中文翻译：

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线粒体相关膜对运动介导的肝脏胰岛素抵抗缓解的贡献：在高脂肪饮食小鼠模型中对比高强度间歇训练与中等强度持续训练

目的线粒体相关膜（MAM）在肝脏胰岛素抵抗（IR）中发挥关键作用。我们的目的是探索 MAM 在通过运动减轻肝脏 IR 方面的潜在作用，并比较不同强度的运动对高脂饮食 (HFD) 小鼠肝脏 MAM 形成的影响。方法雄性 C57BL/6J 小鼠饲喂 HFD 和随机分配接受监督下的高强度间歇训练（HIIT）或中等强度连续训练（MICT）。使用血清甘油三酯/高密度脂蛋白胆固醇比值（TG/HDL-C）、葡萄糖耐量试验（GTT）和胰岛素耐量试验（ITT）评估IR。使用苏木精-伊红 (H&E) 和油红 O 染色观察肝脂肪变性。评估磷脂酰肌醇 3-激酶/蛋白激酶 B/糖原合成酶激酶 3 beta (PI3K-AKT-GSK3β) 信号通路以确定肝脏 IR。通过免疫荧光（电压依赖性阴离子选择性通道 1 [VDAC1] 和肌醇 1,4,5-三磷酸受体 [IP3R] 的共定位）评估 MAM。结果 HFD 治疗 8 周后，肝脏 PI3K/ Akt/GSK3β 信号通路，伴随着肝脏 IP3R-VDAC1 共定位水平的显着降低。 8 周 HIIT 和 MICT 均显着增强 HFD 小鼠肝脏 PI3K/Akt/GSK3β 信号传导和 IP3R-VDAC1 共定位水平，其中 MICT 对肝脏 MAM 形成具有更强的影响。此外，肝脏IP3R-VDAC1的共定位与蛋白激酶B（p-AKT）磷酸化和糖原合成酶激酶3β（p-GSK3β）磷酸化的表达水平呈正相关，而与血清甘油三酯/高水平呈负相关。 ‐密度脂蛋白胆固醇水平。 结论 HFD 诱导的肝脏 MAM 形成减少与肝脏 IR 的发展相关。 HIIT 和 MICT 均能有效促进 HFD 小鼠肝脏 MAM 的形成，其中 MICT 表现出卓越的功效。因此，MAM 可能在运动引起的肝脏 IR 缓解中发挥关键作用。图像