Dataset Information

Exercise prevents substrate overload of liver mitochondria by modification of the compensatory responses during chronic overnutrition

ABSTRACT: Exercise training is a potent treatment of NAFLD and hepatic insulin resistance. Here we provide molecular information about the hepatic mitochondrial metabolism in mice when chronic overnutrition (high-energy diet (HED) for 6 weeks) is combined with exercise training. Training reduced the hepatic triacylglycerol content, fasting insulin, and reversed glucose intolerance. Training modified the hepatic mitochondrial proteome with a decrease in enzymes related to pyruvate metabolism and entry of acetyl-CoA into the TCA cycle. Transcriptome data revealed down-regulation of glucose oxidation and lipogenesis. The mitochondrial respiratory capacity of trained HED-fed mice is increased despite reduced content of complex I. Training decreased diacylglycerol species and JNK phosphorylation, both of which can induce insulin resistance. Increased mitochondrial mass and oxidative capacity of the trained muscle further unburdens the liver from substrate overload. Together, when high fat and carbohydrate intake in mice is accompanied by exercise, the decline of mitochondrial function and insulin resistance can be prevented by modification of mitochondrial acetyl-CoA metabolism.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Skeletal Muscle, Liver

DISEASE(S): Type 2 Diabetes Mellitus,Non-alcoholic Fatty Liver Disease

SUBMITTER: Laxmikanth Kollipara

LAB HEAD: Prof. Dr. Albert Sickmann

PROVIDER: PXD024308 | Pride | 2022-02-16

REPOSITORIES: Pride

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

Hoene Miriam M Kappler Lisa L Kollipara Laxmikanth L Hu Chunxiu C Irmler Martin M Bleher Daniel D Hoffmann Christoph C Beckers Johannes J Hrabě de Angelis Martin M Häring Hans-Ulrich HU Birkenfeld Andreas L AL Peter Andreas A Sickmann Albert A Xu Guowang G Lehmann Rainer R Weigert Cora C

Molecular metabolism 20211022

<h4>Objective</h4>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.<h4>Methods</h4>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 lip ...[more]

PMID: 34695608

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