Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice

IntroductionEmerging evidences suggests that the disrupted branched-chain amino acids (BCAAs) homeostasis and elevated BCAAs promote obesity-related insulin resistance (IR). Exercise improves insulin sensitivity. However, whether BCAAs plays a role in the exercise-attenuated IR remains to be fully i...

Full description

Saved in:
Bibliographic Details
Main Authors: Wei Cao, Yajin Liu, Hao Wei, Yunfeng Dong, Haipeng Sun, Xuejiao Zhang, Junqiang Qiu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-11-01
Series:Frontiers in Nutrition
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2024.1451429/full
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846162489816907776
author Wei Cao
Wei Cao
Yajin Liu
Hao Wei
Yunfeng Dong
Haipeng Sun
Haipeng Sun
Xuejiao Zhang
Xuejiao Zhang
Junqiang Qiu
Junqiang Qiu
author_facet Wei Cao
Wei Cao
Yajin Liu
Hao Wei
Yunfeng Dong
Haipeng Sun
Haipeng Sun
Xuejiao Zhang
Xuejiao Zhang
Junqiang Qiu
Junqiang Qiu
author_sort Wei Cao
collection DOAJ
description IntroductionEmerging evidences suggests that the disrupted branched-chain amino acids (BCAAs) homeostasis and elevated BCAAs promote obesity-related insulin resistance (IR). Exercise improves insulin sensitivity. However, whether BCAAs plays a role in the exercise-attenuated IR remains to be fully investigated.MethodsIn this study, male C57BL/6J mice were induced to become diet-induced obese (DIO) and served as subjects. The initial investigation focused on the impact of exercise on IR and BCAAs. The DIO mice were randomly assigned to either a sedentary group (CON, n = 16) or an exercise group (EX, n = 16). The EX group underwent a 12-week aerobic exercise regimen on a treadmill. After 12-week, plasma BCAAs and branched-chain keto acids (BCKAs) were measured by liquid chromatography-mass spectrometry, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the expression and phosphorylation of BCAAs catabolic proteins, as well as AKT T308 in gastrocnemius muscle and liver tissues, were evaluated using western blotting. Subsequently, the study explored the role of BCAAs in enhancing IR through exercise. Mice were randomly allocated into 4 groups: sedentary group (CON, n = 8), sedentary with BCAAs supplementation group (CON+BCAA, n = 8), exercise group (EX, n = 16), and exercise with BCAAs supplementation group (EX+BCAA, n = 16). The exercise protocol was as above. Mice in the BCAAs supplemented groups received drinking water containing 2% BCAAs. After 12-week, plasma BCAAs and BCKAs were measured, GTT and ITT tests were performed, and the phosphorylation of AKT T308, as well as p70S6K T389 in gastrocnemius muscle and liver, were compared between the EX group and the EX+BCAA group. Additionally, the phosphorylation of AMPKα T172 in both tissues was measured across all four groups.Results12-week aerobic exercise improved insulin sensitivity in DIO mice while inducing BCAAs catabolic protein expression in skeletal muscle and liver, and reducing the plasma BCAAs level. Importantly, BCAAs supplementation elevated the plasma level of BCAAs and counteracted the exercise-attenuated IR. In skeletal muscle and liver tissues, BCAAs supplementation impaired the exercise-improved insulin signaling without enhancing mammalian target of rapamycin activity. AMPK activity was enhanced by aerobic exercise, which was abolished by BCAAs supplementation.ConclusionAerobic exercise attenuated insulin resistance via restoring BCAAs homeostasis and AMPK activity. The impacts of BCAAs intake on the metabolic effects of exercise sheds light on the combined exercise and nutrition intervention strategy for diabetes management.
format Article
id doaj-art-99422d51a9f545dc95508073696dab12
institution Kabale University
issn 2296-861X
language English
publishDate 2024-11-01
publisher Frontiers Media S.A.
record_format Article
series Frontiers in Nutrition
spelling doaj-art-99422d51a9f545dc95508073696dab122024-11-20T09:04:11ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2024-11-011110.3389/fnut.2024.14514291451429Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese miceWei Cao0Wei Cao1Yajin Liu2Hao Wei3Yunfeng Dong4Haipeng Sun5Haipeng Sun6Xuejiao Zhang7Xuejiao Zhang8Junqiang Qiu9Junqiang Qiu10Department of Exercise Biochemistry, Exercise Science School, Beijing Sport University, Beijing, ChinaCollege of Sports and Health, Shandong Sport University, Rizhao, ChinaChu Hsien-I Memorial Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaDepartment of Exercise Biochemistry, Exercise Science School, Beijing Sport University, Beijing, ChinaDepartment of Exercise Biochemistry, Exercise Science School, Beijing Sport University, Beijing, ChinaChu Hsien-I Memorial Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaCenter for Cardiovascular Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaChu Hsien-I Memorial Hospital, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, ChinaCenter for Cardiovascular Diseases, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin Medical University, Tianjin, ChinaDepartment of Exercise Biochemistry, Exercise Science School, Beijing Sport University, Beijing, ChinaBeijing Sports Nutrition Engineering Research Center, Beijing, ChinaIntroductionEmerging evidences suggests that the disrupted branched-chain amino acids (BCAAs) homeostasis and elevated BCAAs promote obesity-related insulin resistance (IR). Exercise improves insulin sensitivity. However, whether BCAAs plays a role in the exercise-attenuated IR remains to be fully investigated.MethodsIn this study, male C57BL/6J mice were induced to become diet-induced obese (DIO) and served as subjects. The initial investigation focused on the impact of exercise on IR and BCAAs. The DIO mice were randomly assigned to either a sedentary group (CON, n = 16) or an exercise group (EX, n = 16). The EX group underwent a 12-week aerobic exercise regimen on a treadmill. After 12-week, plasma BCAAs and branched-chain keto acids (BCKAs) were measured by liquid chromatography-mass spectrometry, glucose tolerance test (GTT) and insulin tolerance test (ITT) were performed, and the expression and phosphorylation of BCAAs catabolic proteins, as well as AKT T308 in gastrocnemius muscle and liver tissues, were evaluated using western blotting. Subsequently, the study explored the role of BCAAs in enhancing IR through exercise. Mice were randomly allocated into 4 groups: sedentary group (CON, n = 8), sedentary with BCAAs supplementation group (CON+BCAA, n = 8), exercise group (EX, n = 16), and exercise with BCAAs supplementation group (EX+BCAA, n = 16). The exercise protocol was as above. Mice in the BCAAs supplemented groups received drinking water containing 2% BCAAs. After 12-week, plasma BCAAs and BCKAs were measured, GTT and ITT tests were performed, and the phosphorylation of AKT T308, as well as p70S6K T389 in gastrocnemius muscle and liver, were compared between the EX group and the EX+BCAA group. Additionally, the phosphorylation of AMPKα T172 in both tissues was measured across all four groups.Results12-week aerobic exercise improved insulin sensitivity in DIO mice while inducing BCAAs catabolic protein expression in skeletal muscle and liver, and reducing the plasma BCAAs level. Importantly, BCAAs supplementation elevated the plasma level of BCAAs and counteracted the exercise-attenuated IR. In skeletal muscle and liver tissues, BCAAs supplementation impaired the exercise-improved insulin signaling without enhancing mammalian target of rapamycin activity. AMPK activity was enhanced by aerobic exercise, which was abolished by BCAAs supplementation.ConclusionAerobic exercise attenuated insulin resistance via restoring BCAAs homeostasis and AMPK activity. The impacts of BCAAs intake on the metabolic effects of exercise sheds light on the combined exercise and nutrition intervention strategy for diabetes management.https://www.frontiersin.org/articles/10.3389/fnut.2024.1451429/fullaerobic exercisebranched-chain amino acidsmammalian target of rapamycinAMP-activated protein kinaseinsulin resistance
spellingShingle Wei Cao
Wei Cao
Yajin Liu
Hao Wei
Yunfeng Dong
Haipeng Sun
Haipeng Sun
Xuejiao Zhang
Xuejiao Zhang
Junqiang Qiu
Junqiang Qiu
Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
Frontiers in Nutrition
aerobic exercise
branched-chain amino acids
mammalian target of rapamycin
AMP-activated protein kinase
insulin resistance
title Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
title_full Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
title_fullStr Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
title_full_unstemmed Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
title_short Aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
title_sort aerobic exercise attenuates insulin resistance via restoring branched chain amino acids homeostasis in obese mice
topic aerobic exercise
branched-chain amino acids
mammalian target of rapamycin
AMP-activated protein kinase
insulin resistance
url https://www.frontiersin.org/articles/10.3389/fnut.2024.1451429/full
work_keys_str_mv AT weicao aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT weicao aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT yajinliu aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT haowei aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT yunfengdong aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT haipengsun aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT haipengsun aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT xuejiaozhang aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT xuejiaozhang aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT junqiangqiu aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice
AT junqiangqiu aerobicexerciseattenuatesinsulinresistanceviarestoringbranchedchainaminoacidshomeostasisinobesemice