How exercise can protect against obesity-related diseases

Sport not only trains the muscles, but can also prevent the development of fatty liver. A new study by the German Center for Diabetes Research (DZD), Helmholtz Munich and the University Hospital Tübingen shows which molecular adaptations can be observed, especially in the liver mitochondria. The study has now been published in Molecular Metabolism.

One in four people worldwide suffers from non-alcoholic liver disease (NAFLD, also known as metabolic liver disease MAFLD). Those affected often have type 2 diabetes and an increased risk of liver cirrhosis and cardiovascular disease. In addition, NAFLD has been linked to increased mortality. An imbalance between energy intake and consumption is discussed as the cause of the disease. This leads to fat deposits in the liver and over time impairs the function of the mitochondria * – both risk factors for the development of hepatic insulin resistance and liver inflammation.

How exercise changes the way the liver adapts to increased energy intake

Lifestyle changes with increased physical activity are recommended for the prevention and treatment of NAFLD. Scientists from the Institute for Clinical Chemistry and Pathobiochemistry at the University Hospital Tübingen and the Institute for Diabetes Research and Metabolic Diseases (IDM) at Helmholtz Munich at the University of Tübingen examined the extent to which regular exercise changes the liver’s adaptation to increased energy consumption. The researchers cooperated with the Institute for Experimental Genetics (IEG) at Helmholtz Munich, the Leibniz Institute for Analytical Sciences in Dortmund and the Dalian Institute of Chemical Physics in China.

Exercise can prevent fatty liver from overeating

In the Dr. Miriam Hoene and Dr. Lisa Kappler conducted study, mice were fed a high-energy diet. Some of the mice also received regular treadmill exercise. After the six-week intervention, the researchers examined the animals’ liver and muscles for changes in the transcriptome, mitochondrial proteome, lipid composition and mitochondrial function.

The results showed that exercise regulates important enzymes involved in the breakdown of glucose and fructose in the liver and the mitochondrial pyruvate metabolism. In this way, the substrate load for mitochondrial respiration and lipid synthesis can be reduced. As a result, less fat is stored in the liver – and certain lipids such as diacylglycerol species are lowered. In addition, glucose control improves in the physically trained mice. In addition, an increased breathing capacity of the skeletal muscles relieves the metabolic load in the liver.

The systems biology data offer a comprehensive insight into the molecular adaptation of the liver and muscles to a high-energy diet, training and combinatorial effects. “The results fit very well with the approaches of ongoing clinical studies in which inhibitors are tested against some of the targets found here, such as the mitochondrial pyruvate transporter,” says DZD scientist Prof. Dr. Cora Weigert, head of the study and professor for molecular diabetology at the University Hospital Tübingen. “They also show that regular physical activity regulates many points of attack and, at the same time, important nodes of metabolic pathways, an effect that cannot be achieved with monotherapy.”

* Mitochondria

The mitochondria have the task of making energy available to the cell, which happens through cell respiration. This is a metabolic process in which the energy stored in glucose and other organic substances is obtained by breaking the chemical bond, which ultimately results in adenosine triphosphate or ATP. This is the most important energy molecule in the body. Mitochondria are therefore also considered to be the power plants of the cell.

Reference: “Sport prevents fatty liver by modifying the compensatory reaction of the mitochondrial metabolism to excessive substrate availability” by Miriam Hoene, Lisa Kappler, Laxmikanth Kollipara, Chunxiu Hu, Martin Irmler, Daniel Bleher, Christoph Hoffmann, Johannes Beckers, Martin Hrabe de Angelis , Hans-Ulrich Häring, Andreas L.Birkenfeld, Andreas Peter, Albert Sickmann, Guowang Xu, Rainer Lehmann and Cora Weigert, October 22, 2021, Molecular Metabolism.
DOI: 10.1016 / j.molmet.2021.101359

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