Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats

Abstract Background Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated th...

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Main Authors: Fuyao Yu, Chuan Xing, Yiping Fan, Yanping Liu, Peng Su, Qiuhua Yang, Yanbin Dong, Yang Hou, Shinong Pan
Format: Article
Language:English
Published: BMC 2023-10-01
Series:Diabetology & Metabolic Syndrome
Subjects:
Online Access:https://doi.org/10.1186/s13098-023-01183-x
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author Fuyao Yu
Chuan Xing
Yiping Fan
Yanping Liu
Peng Su
Qiuhua Yang
Yanbin Dong
Yang Hou
Shinong Pan
author_facet Fuyao Yu
Chuan Xing
Yiping Fan
Yanping Liu
Peng Su
Qiuhua Yang
Yanbin Dong
Yang Hou
Shinong Pan
author_sort Fuyao Yu
collection DOAJ
description Abstract Background Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated the effects of moderate aerobic exercise and/or metformin on histological IMAT parameters in non-streptozotocin-induced prediabetes. Methods Male Wistar rats with prediabetes fed a high-fat diet and high-sugar drinks were randomly assigned to high-fat diet (PRE), metformin (MET), moderate aerobic exercise (EXE), combined therapy (EMC), or EMC + compound-c (EMA) groups for 4 weeks. Multimodal magnetic resonance imaging (MRI) was then performed, and tissue-specific inflammation and energy and lipid metabolism were evaluated in IMAT. Results The EXE group had lower inflammatory factor levels, lipid metabolism, and mitochondrial oxidative stress, and shorter IMAT adipocyte diameters than the MET group. The MET group exhibited lower IL-1β and Plin5 expression than the PRE group. Furthermore, the IMAT of the EMC group had lower TNF-α and phosphorylated NF-κB levels and higher GLUT1 and GLUT4 expression than the PRE group. Multimodal MRI revealed significant changes in transverse-relaxation time 2, apparent diffusion coefficient, and fractional anisotropy values in the IMAT and muscles, as well as lower IMAT% values in the EXE and EMC groups than in the MET and PRE groups. Conclusion Moderate aerobic exercise training can effectively improve IMAT function and structure via the AMP-activated protein kinase pathway in prediabetes. Combining metformin with moderate aerobic exercise might elicit modest synergy, and metformin does not counterbalance the beneficial effects of exercise.
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spelling doaj.art-2ad1b296f7964e898f099cd3f60dfe002023-11-05T12:25:25ZengBMCDiabetology & Metabolic Syndrome1758-59962023-10-0115111710.1186/s13098-023-01183-xAerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic ratsFuyao Yu0Chuan Xing1Yiping Fan2Yanping Liu3Peng Su4Qiuhua Yang5Yanbin Dong6Yang Hou7Shinong Pan8Department of Radiology, Shengjing Hospital of China Medical UniversityDepartment of Endocrinology, The People’s Hospital of Liaoning ProvinceDepartment of Nuclear Medicine, The Fourth Affiliated Hospital of China Medical UniversityDepartment of Gastroenterology and Medical Research Center, Shengjing Hospital of China Medical UniversityDepartment of Gastroenterology and Medical Research Center, Shengjing Hospital of China Medical UniversityVascular Biology Center, Medical College of Georgia, Augusta UniversityDepartment of Medicine, Georgia Prevention Institute, Medical College of GeorgiaDepartment of Radiology, Shengjing Hospital of China Medical UniversityDepartment of Radiology, Shengjing Hospital of China Medical UniversityAbstract Background Physical exercise is the first-line intervention for prediabetes, and metformin is the most widely used oral insulin-sensitizing agent. Moreover, intermuscular adipose tissue (IMAT) directly affects insulin resistance by helping maintain glucose homeostasis. Here, we evaluated the effects of moderate aerobic exercise and/or metformin on histological IMAT parameters in non-streptozotocin-induced prediabetes. Methods Male Wistar rats with prediabetes fed a high-fat diet and high-sugar drinks were randomly assigned to high-fat diet (PRE), metformin (MET), moderate aerobic exercise (EXE), combined therapy (EMC), or EMC + compound-c (EMA) groups for 4 weeks. Multimodal magnetic resonance imaging (MRI) was then performed, and tissue-specific inflammation and energy and lipid metabolism were evaluated in IMAT. Results The EXE group had lower inflammatory factor levels, lipid metabolism, and mitochondrial oxidative stress, and shorter IMAT adipocyte diameters than the MET group. The MET group exhibited lower IL-1β and Plin5 expression than the PRE group. Furthermore, the IMAT of the EMC group had lower TNF-α and phosphorylated NF-κB levels and higher GLUT1 and GLUT4 expression than the PRE group. Multimodal MRI revealed significant changes in transverse-relaxation time 2, apparent diffusion coefficient, and fractional anisotropy values in the IMAT and muscles, as well as lower IMAT% values in the EXE and EMC groups than in the MET and PRE groups. Conclusion Moderate aerobic exercise training can effectively improve IMAT function and structure via the AMP-activated protein kinase pathway in prediabetes. Combining metformin with moderate aerobic exercise might elicit modest synergy, and metformin does not counterbalance the beneficial effects of exercise.https://doi.org/10.1186/s13098-023-01183-xAdipose tissueMetforminAerobic exercisePrediabetesMultimodal imagingMagnetic-resonance imaging
spellingShingle Fuyao Yu
Chuan Xing
Yiping Fan
Yanping Liu
Peng Su
Qiuhua Yang
Yanbin Dong
Yang Hou
Shinong Pan
Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
Diabetology & Metabolic Syndrome
Adipose tissue
Metformin
Aerobic exercise
Prediabetes
Multimodal imaging
Magnetic-resonance imaging
title Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
title_full Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
title_fullStr Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
title_full_unstemmed Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
title_short Aerobic exercise and metformin on intermuscular adipose tissue (IMAT): insights from multimodal MRI and histological changes in prediabetic rats
title_sort aerobic exercise and metformin on intermuscular adipose tissue imat insights from multimodal mri and histological changes in prediabetic rats
topic Adipose tissue
Metformin
Aerobic exercise
Prediabetes
Multimodal imaging
Magnetic-resonance imaging
url https://doi.org/10.1186/s13098-023-01183-x
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