HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation

Abstract Objective Compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the mechanisms by which these two exercise modalities influence gut microbiota structur...

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Main Authors: Dongkun Deng, Lin Xu, Yufei Liu, Chang Li, Qingfeng Jiang, Jiaming Shi, Shuo Feng, Yunhua Lin
Format: Article
Language:English
Published: BMC 2025-04-01
Series:Lipids in Health and Disease
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Online Access:https://doi.org/10.1186/s12944-025-02565-y
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author Dongkun Deng
Lin Xu
Yufei Liu
Chang Li
Qingfeng Jiang
Jiaming Shi
Shuo Feng
Yunhua Lin
author_facet Dongkun Deng
Lin Xu
Yufei Liu
Chang Li
Qingfeng Jiang
Jiaming Shi
Shuo Feng
Yunhua Lin
author_sort Dongkun Deng
collection DOAJ
description Abstract Objective Compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the mechanisms by which these two exercise modalities influence gut microbiota structure, bile acid metabolism, and intestinal barrier function, as well as their regulatory roles in hepatic lipid synthesis and oxidative dynamics. Explore the synergistic effects of exercise-mediated mitochondrial fusion remodeling and leptin signaling, elucidate the causal relationship between gut-derived factors and hepatic metabolic reprogramming, and reveal the potential multi-scale and cross-organ dominant mechanisms of exercise, providing a theoretical basis for systematically comparing the effects of different exercise modalities. Methods Thirty-two male rats were randomly divided into NFD (n = 8) and HFD (n = 24) groups and fed normal chow and high-fat chow, respectively. After eight weeks, the HFD group was randomly divided into three groups: (1) MICT-8; (2) HIIT-8; and (3) HFD-8. At the end of the experiment, blood, liver, ileum, and skeletal muscle samples were collected for analysis of the rats' baseline conditions, mitochondrial function, hepatic lipid metabolism, bile acid pathway and gut microbiota, and synthesis of analyses. Results Both modes of exercise ameliorated metabolic dysregulation and attenuated pathological progression, insulin resistance, and liver fat accumulation in rats with MASLD. Furthermore, both interventions counteracted HFD-induced intestinal barrier dysfunction and restored gut-liver axis homeostasis. HIIT and MICT also upregulated bile acid-related gene expression modulated butyrate-producing bacterial taxa, and adjusted the abundance of butyrate-generating bacteria. Conclusion Both HIIT and MICT improved lipid metabolism in MASLD rats and the difference between the HIIT and MICT groups was not statistically significant. It is noteworthy that HIIT was more effective in improving mitochondrial function in MASLD than MICT (P < 0.001). Graphical Abstract Image annotations: MICT: Moderate-intensity Continuous Training; HIIT: High-intensity Interval Training; HFD: high-fat diet; SCFAS: short-chain fatty acid; FXR: farnesoid X receptor; LXRα: liver X receptor α; SREBP-1c: sterol regulatory element binding protein 1c; CPT-1: carnitine palmitoyltransferase 1; PPARα: peroxisome proliferator-activated receptor α; PGC-1α: peroxisome proliferator-activated receptor γ coactivator 1α; CS: citrate synthase; COX IV: cytochrome c oxidase IV; PINK1: PTEN-induced putative kinase 1; Parkin: Parkinson protein 2; Mfn1: mitofusin 1; Mfn2: mitofusin 2; Fis1: Fission 1 protein. Created with figdraw.com.
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spelling doaj-art-ac29df0e41d14697babe10cdc8c5ee672025-08-20T02:28:11ZengBMCLipids in Health and Disease1476-511X2025-04-0124112010.1186/s12944-025-02565-yHIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuationDongkun Deng0Lin Xu1Yufei Liu2Chang Li3Qingfeng Jiang4Jiaming Shi5Shuo Feng6Yunhua Lin7College of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityCollege of Sports and Human Sciences, Graduate School, Harbin Sport UniversityAbstract Objective Compare the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on metabolic dysfunction-associated steatotic liver disease (MASLD), focusing on the mechanisms by which these two exercise modalities influence gut microbiota structure, bile acid metabolism, and intestinal barrier function, as well as their regulatory roles in hepatic lipid synthesis and oxidative dynamics. Explore the synergistic effects of exercise-mediated mitochondrial fusion remodeling and leptin signaling, elucidate the causal relationship between gut-derived factors and hepatic metabolic reprogramming, and reveal the potential multi-scale and cross-organ dominant mechanisms of exercise, providing a theoretical basis for systematically comparing the effects of different exercise modalities. Methods Thirty-two male rats were randomly divided into NFD (n = 8) and HFD (n = 24) groups and fed normal chow and high-fat chow, respectively. After eight weeks, the HFD group was randomly divided into three groups: (1) MICT-8; (2) HIIT-8; and (3) HFD-8. At the end of the experiment, blood, liver, ileum, and skeletal muscle samples were collected for analysis of the rats' baseline conditions, mitochondrial function, hepatic lipid metabolism, bile acid pathway and gut microbiota, and synthesis of analyses. Results Both modes of exercise ameliorated metabolic dysregulation and attenuated pathological progression, insulin resistance, and liver fat accumulation in rats with MASLD. Furthermore, both interventions counteracted HFD-induced intestinal barrier dysfunction and restored gut-liver axis homeostasis. HIIT and MICT also upregulated bile acid-related gene expression modulated butyrate-producing bacterial taxa, and adjusted the abundance of butyrate-generating bacteria. Conclusion Both HIIT and MICT improved lipid metabolism in MASLD rats and the difference between the HIIT and MICT groups was not statistically significant. It is noteworthy that HIIT was more effective in improving mitochondrial function in MASLD than MICT (P < 0.001). Graphical Abstract Image annotations: MICT: Moderate-intensity Continuous Training; HIIT: High-intensity Interval Training; HFD: high-fat diet; SCFAS: short-chain fatty acid; FXR: farnesoid X receptor; LXRα: liver X receptor α; SREBP-1c: sterol regulatory element binding protein 1c; CPT-1: carnitine palmitoyltransferase 1; PPARα: peroxisome proliferator-activated receptor α; PGC-1α: peroxisome proliferator-activated receptor γ coactivator 1α; CS: citrate synthase; COX IV: cytochrome c oxidase IV; PINK1: PTEN-induced putative kinase 1; Parkin: Parkinson protein 2; Mfn1: mitofusin 1; Mfn2: mitofusin 2; Fis1: Fission 1 protein. Created with figdraw.com.https://doi.org/10.1186/s12944-025-02565-yMASLDMitochondrial functionLipid metabolismOxidative stressGut-liver axis
spellingShingle Dongkun Deng
Lin Xu
Yufei Liu
Chang Li
Qingfeng Jiang
Jiaming Shi
Shuo Feng
Yunhua Lin
HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation
Lipids in Health and Disease
MASLD
Mitochondrial function
Lipid metabolism
Oxidative stress
Gut-liver axis
title HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation
title_full HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation
title_fullStr HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation
title_full_unstemmed HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation
title_short HIIT versus MICT in MASLD: mechanisms mediated by gut-liver axis crosstalk, mitochondrial dynamics remodeling, and adipokine signaling attenuation
title_sort hiit versus mict in masld mechanisms mediated by gut liver axis crosstalk mitochondrial dynamics remodeling and adipokine signaling attenuation
topic MASLD
Mitochondrial function
Lipid metabolism
Oxidative stress
Gut-liver axis
url https://doi.org/10.1186/s12944-025-02565-y
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