Mitochondria‐associated membranes contribution to exercise‐mediated alleviation of hepatic insulin resistance: Contrasting high‐intensity interval training with moderate‐intensity continuous training in a high‐fat diet mouse model

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Main Authors: Xi Li, Jun Yang Yang, Wen Zhi Hu, YuXin Ruan, Hong Ying Chen, Qiang Zhang, Zhe Zhang, Zhe Shu Ding
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Published: Wiley 2024
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author Xi Li
Jun Yang Yang
Wen Zhi Hu
YuXin Ruan
Hong Ying Chen
Qiang Zhang
Zhe Zhang
Zhe Shu Ding
author_facet Xi Li
Jun Yang Yang
Wen Zhi Hu
YuXin Ruan
Hong Ying Chen
Qiang Zhang
Zhe Zhang
Zhe Shu Ding
Xi Li
Jun Yang Yang
Wen Zhi Hu
YuXin Ruan
Hong Ying Chen
Qiang Zhang
Zhe Zhang
Zhe Shu Ding
collection Wiley Open Access
contents Mitochondria‐associated membranes contribution to exercise‐mediated alleviation of hepatic insulin resistance: Contrasting high‐intensity interval training with moderate‐intensity continuous training in a high‐fat diet mouse model Xi Li Jun Yang Yang Wen Zhi Hu YuXin Ruan Hong Ying Chen Qiang Zhang Zhe Zhang Zhe Shu Ding Journal of Diabetes AbstractObjectiveMitochondria‐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 10.1111/1753-0407.13540 http://creativecommons.org/licenses/by/4.0/
doi_str_mv 10.1111/1753-0407.13540
format Artículo Open Access
id wiley_oa_10_1111_1753_0407_13540
institution Wiley Open Access
license_str_mv http://creativecommons.org/licenses/by/4.0/
publishDate 2024
publisher Wiley
record_format wiley_oa
spellingShingle Mitochondria‐associated membranes contribution to exercise‐mediated alleviation of hepatic insulin resistance: Contrasting high‐intensity interval training with moderate‐intensity continuous training in a high‐fat diet mouse model
Xi Li
Jun Yang Yang
Wen Zhi Hu
YuXin Ruan
Hong Ying Chen
Qiang Zhang
Zhe Zhang
Zhe Shu Ding
Journal of Diabetes
Mitochondria‐associated membranes contribution to exercise‐mediated alleviation of hepatic insulin resistance: Contrasting high‐intensity interval training with moderate‐intensity continuous training in a high‐fat diet mouse model Xi Li Jun Yang Yang Wen Zhi Hu YuXin Ruan Hong Ying Chen Qiang Zhang Zhe Zhang Zhe Shu Ding Journal of Diabetes AbstractObjectiveMitochondria‐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 10.1111/1753-0407.13540 http://creativecommons.org/licenses/by/4.0/
title Mitochondria‐associated membranes contribution to exercise‐mediated alleviation of hepatic insulin resistance: Contrasting high‐intensity interval training with moderate‐intensity continuous training in a high‐fat diet mouse model
topic Journal of Diabetes
url https://onlinelibrary.wiley.com/doi/10.1111/1753-0407.13540