https://www.sciencedirect.com/science/article/pii/S2212877821002064

JavaScript is disabled on your browser. Please enable JavaScript to
use all the features on this page. [1642719719] Skip to main content
Skip to article
Elsevier logo

  * Journals & Books

  *  
  *  

RegisterSign in
Sign inRegister

  * Journals & Books

  * Help

  * View PDF
  * Download full issue

[                    ]
Elsevier

Molecular Metabolism

Volume 54, December 2021, 101359
Molecular Metabolism

Original Article
Exercise prevents fatty liver by modifying the compensatory response
of mitochondrial metabolism to excess substrate availability

Author links open overlay panelMiriamHoene^1^11LisaKappler^1^11
LaxmikanthKollipara^2ChunxiuHu^3MartinIrmler^4DanielBleher^1Christoph
Hoffmann^1JohannesBeckers^4^5^6MartinHrabe de Angelis^4^5^6
Hans-UlrichHaring^6^7Andreas L.Birkenfeld^6^7^8AndreasPeter^1^6^7
AlbertSickmann^2^9^10GuowangXu^3RainerLehmann^1^6^7CoraWeigert^1^6^7
Show more
Share
Cite
https://doi.org/10.1016/j.molmet.2021.101359Get rights and content
Under a Creative Commons license
open access

Highlights

*

    High-energy diet promotes mitochondrial respiration in liver
    independent of training.

*

    High-energy diet combined with training disconnects substrate
    oxidation from lipid synthesis.

*

    High-energy diet combined with training reduces complex I
    formation in the liver.

*

    Trained skeletal muscle unburdens the liver from substrate
    overload.

*

    Comprehensive resource of mitochondrial adaptations to
    high-energy diet and training.

Abstract

Objective

Liver mitochondria adapt to high-calorie intake. We investigated how
exercise alters the early compensatory response of mitochondria, thus
preventing fatty liver disease as a long-term consequence of
overnutrition.

Methods

We compared the effects of a steatogenic high-energy diet (HED) for
six weeks on mitochondrial metabolism of sedentary and
treadmill-trained C57BL/6N mice. We applied multi-OMICs analyses to
study the alterations in the proteome, transcriptome, and lipids in
isolated mitochondria of liver and skeletal muscle as well as in
whole tissue and examined the functional consequences by
high-resolution respirometry.

Results

HED increased the respiratory capacity of isolated liver
mitochondria, both in sedentary and in trained mice. However,
proteomics analysis of the mitochondria and transcriptomics indicated
that training modified the adaptation of the hepatic metabolism to
HED on the level of respiratory complex I, glucose oxidation,
pyruvate and acetyl-CoA metabolism, and lipogenesis. Training also
counteracted the HED-induced glucose intolerance, the increase in
fasting insulin, and in liver fat by lowering diacylglycerol species
and c-Jun N-terminal kinase (JNK) phosphorylation in the livers of
trained HED-fed mice, two mechanisms that can reverse hepatic insulin
resistance. In skeletal muscle, the combination of HED and training
improved the oxidative capacity to a greater extent than training
alone by increasing respiration of isolated mitochondria and total
mitochondrial protein content.

Conclusion

We provide a comprehensive insight into the early adaptations of
mitochondria in the liver and skeletal muscle to HED and endurance
training. Our results suggest that exercise disconnects the
HED-induced increase in mitochondrial substrate oxidation from
pyruvate and acetyl-CoA-driven lipid synthesis. This could contribute
to the prevention of deleterious long-term effects of high fat and
sugar intake on hepatic mitochondrial function and insulin
sensitivity.

  * Previous article in issue
  * Next article in issue

Keywords

Exercise
Mitochondrial supercomplexes
Acetyl-CoA
MAFLD
Lipidomics
Proteomics
Recommended articlesCiting articles (0)

^11

    Miriam Hoene and Lisa Kappler contributed equally.

(c) 2021 The Author(s). Published by Elsevier GmbH.

Recommended articles

No articles found.

Citing articles

Article Metrics

View article metrics
Elsevier logo

  * About ScienceDirect
  * Remote access
  * Shopping cart
  * Advertise
  * Contact and support
  * Terms and conditions
  * Privacy policy

We use cookies to help provide and enhance our service and tailor
content and ads. By continuing you agree to the use of cookies.

Copyright (c) 2022 Elsevier B.V. or its licensors or contributors. 
ScienceDirect (r) is a registered trademark of Elsevier B.V.

ScienceDirect (r) is a registered trademark of Elsevier B.V.

RELX group home page