Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue

The aim of the present work was to study the consequences of chronic exercise training on factors involved in the regulation of mitochondrial remodeling and biogenesis, as well as the ability to produce energy and improve insulin sensitivity and glucose uptake in rat brown adipose tissue (BAT). Male...

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Main Authors: Natalia de las Heras, Mercedes Klett-Mingo, Sandra Ballesteros, Beatriz Martín-Fernández, Óscar Escribano, Javier Blanco-Rivero, Gloria Balfagón, Marta L. Hribal, Manuel Benito, Vicente Lahera, Almudena Gómez-Hernández
Format: Article
Language:English
Published: Frontiers Media S.A. 2018-08-01
Series:Frontiers in Physiology
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fphys.2018.01122/full
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author Natalia de las Heras
Mercedes Klett-Mingo
Sandra Ballesteros
Beatriz Martín-Fernández
Óscar Escribano
Óscar Escribano
Javier Blanco-Rivero
Gloria Balfagón
Marta L. Hribal
Manuel Benito
Manuel Benito
Vicente Lahera
Almudena Gómez-Hernández
Almudena Gómez-Hernández
author_facet Natalia de las Heras
Mercedes Klett-Mingo
Sandra Ballesteros
Beatriz Martín-Fernández
Óscar Escribano
Óscar Escribano
Javier Blanco-Rivero
Gloria Balfagón
Marta L. Hribal
Manuel Benito
Manuel Benito
Vicente Lahera
Almudena Gómez-Hernández
Almudena Gómez-Hernández
author_sort Natalia de las Heras
collection DOAJ
description The aim of the present work was to study the consequences of chronic exercise training on factors involved in the regulation of mitochondrial remodeling and biogenesis, as well as the ability to produce energy and improve insulin sensitivity and glucose uptake in rat brown adipose tissue (BAT). Male Wistar rats were divided into two groups: (1) control group (C; n = 10) and (2) exercise-trained rats (ET; n = 10) for 8 weeks on a motor treadmill (five times per week for 50 min). Exercise training reduced body weight, plasma insulin, and oxidized LDL concentrations. Protein expression of ATP-independent metalloprotease (OMA1), short optic atrophy 1 (S-OPA1), and dynamin-related protein 1 (DRP1) in BAT increased in trained rats, and long optic atrophy 1 (L-OPA1) and mitofusin 1 (MFN1) expression decreased. BAT expression of nuclear respiratory factor type 1 (NRF1) and mitochondrial transcription factor A (TFAM), the main factors involved in mitochondrial biogenesis, was higher in trained rats compared to controls. Exercise training increased protein expression of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and AMP-activated protein kinase (pAMPK/AMPK ratio) in BAT. In addition, training increased carnitine palmitoyltransferase II (CPT II), mitochondrial F1 ATP synthase α-chain, mitochondrial malate dehydrogenase 2 (mMDH) and uncoupling protein (UCP) 1,2,3 expression in BAT. Moreover, exercise increased insulin receptor (IR) ratio (IRA/IRB ratio), IRA-insulin-like growth factor 1 receptor (IGF-1R) hybrids and p42/44 activation, and decreased IGF-1R expression and IR substrate 1 (p-IRS-1) (S307) indicating higher insulin sensitivity and favoring glucose uptake in BAT in response to chronic exercise training. In summary, the present study indicates that chronic exercise is able to improve the energetic profile of BAT in terms of increased mitochondrial function and insulin sensitivity.
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spelling doaj.art-bc25b29289ba4109b9d798cb3d0723232022-12-21T17:13:10ZengFrontiers Media S.A.Frontiers in Physiology1664-042X2018-08-01910.3389/fphys.2018.01122394824Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose TissueNatalia de las Heras0Mercedes Klett-Mingo1Sandra Ballesteros2Beatriz Martín-Fernández3Óscar Escribano4Óscar Escribano5Javier Blanco-Rivero6Gloria Balfagón7Marta L. Hribal8Manuel Benito9Manuel Benito10Vicente Lahera11Almudena Gómez-Hernández12Almudena Gómez-Hernández13Department of Physiology, School of Medicine, Complutense University of Madrid, Madrid, SpainDepartment of Physiology, School of Medicine, Complutense University of Madrid, Madrid, SpainDepartment of Physiology, School of Medicine, Complutense University of Madrid, Madrid, SpainDepartment of Physiology, School of Medicine, Complutense University of Madrid, Madrid, SpainDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, Complutense University of Madrid, Madrid, SpainCIBER of Diabetes and Associated Metabolic Diseases, Barcelona, SpainDepartment of Physiology, School of Medicine, Autonomous University of Madrid, Madrid, SpainDepartment of Physiology, School of Medicine, Autonomous University of Madrid, Madrid, SpainDepartment of Medical and Surgical Sciences, Magna Græcia University of Catanzaro, Catanzaro, ItalyDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, Complutense University of Madrid, Madrid, SpainCIBER of Diabetes and Associated Metabolic Diseases, Barcelona, SpainDepartment of Physiology, School of Medicine, Complutense University of Madrid, Madrid, SpainDepartment of Biochemistry and Molecular Biology II, School of Pharmacy, Complutense University of Madrid, Madrid, SpainCIBER of Diabetes and Associated Metabolic Diseases, Barcelona, SpainThe aim of the present work was to study the consequences of chronic exercise training on factors involved in the regulation of mitochondrial remodeling and biogenesis, as well as the ability to produce energy and improve insulin sensitivity and glucose uptake in rat brown adipose tissue (BAT). Male Wistar rats were divided into two groups: (1) control group (C; n = 10) and (2) exercise-trained rats (ET; n = 10) for 8 weeks on a motor treadmill (five times per week for 50 min). Exercise training reduced body weight, plasma insulin, and oxidized LDL concentrations. Protein expression of ATP-independent metalloprotease (OMA1), short optic atrophy 1 (S-OPA1), and dynamin-related protein 1 (DRP1) in BAT increased in trained rats, and long optic atrophy 1 (L-OPA1) and mitofusin 1 (MFN1) expression decreased. BAT expression of nuclear respiratory factor type 1 (NRF1) and mitochondrial transcription factor A (TFAM), the main factors involved in mitochondrial biogenesis, was higher in trained rats compared to controls. Exercise training increased protein expression of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) and AMP-activated protein kinase (pAMPK/AMPK ratio) in BAT. In addition, training increased carnitine palmitoyltransferase II (CPT II), mitochondrial F1 ATP synthase α-chain, mitochondrial malate dehydrogenase 2 (mMDH) and uncoupling protein (UCP) 1,2,3 expression in BAT. Moreover, exercise increased insulin receptor (IR) ratio (IRA/IRB ratio), IRA-insulin-like growth factor 1 receptor (IGF-1R) hybrids and p42/44 activation, and decreased IGF-1R expression and IR substrate 1 (p-IRS-1) (S307) indicating higher insulin sensitivity and favoring glucose uptake in BAT in response to chronic exercise training. In summary, the present study indicates that chronic exercise is able to improve the energetic profile of BAT in terms of increased mitochondrial function and insulin sensitivity.https://www.frontiersin.org/article/10.3389/fphys.2018.01122/fullmitochondrial dynamicinsulin sensitivityexercisebrown adipose tissueUCPs
spellingShingle Natalia de las Heras
Mercedes Klett-Mingo
Sandra Ballesteros
Beatriz Martín-Fernández
Óscar Escribano
Óscar Escribano
Javier Blanco-Rivero
Gloria Balfagón
Marta L. Hribal
Manuel Benito
Manuel Benito
Vicente Lahera
Almudena Gómez-Hernández
Almudena Gómez-Hernández
Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue
Frontiers in Physiology
mitochondrial dynamic
insulin sensitivity
exercise
brown adipose tissue
UCPs
title Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue
title_full Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue
title_fullStr Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue
title_full_unstemmed Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue
title_short Chronic Exercise Improves Mitochondrial Function and Insulin Sensitivity in Brown Adipose Tissue
title_sort chronic exercise improves mitochondrial function and insulin sensitivity in brown adipose tissue
topic mitochondrial dynamic
insulin sensitivity
exercise
brown adipose tissue
UCPs
url https://www.frontiersin.org/article/10.3389/fphys.2018.01122/full
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