How Exercise Can Protect Against Fatty Liver Diseases

Exercise not only trains the muscles, but can also prevent the development of fatty liver disease. A new study from the German Diabetes Research Center (DZD), Helmholtz Munich and the University Hospital Tübingen shows what molecular adaptations, especially of hepatic mitochondria, can be seen in this process. The study has just been published in Molecular metabolism.

Globally, one in four people has non-alcoholic liver disease (NAFLD, also known as MAFLD metabolic liver disease). Those affected often have type 2 diabetes as well as an increased risk of liver cirrhosis and cardiovascular disease. Additionally, NAFLD is associated with increased mortality. An imbalance between energy intake and consumption is discussed as a cause of the disease. This leads to fatty deposits in the liver and, over time, impairs the functioning of the mitochondria *, two risk factors for the development of hepatic insulin resistance and inflammation of the liver.

How exercise alters the liver’s adaptation to increased energy intake

To prevent and treat NAFLD, lifestyle modification with increased physical activity is recommended. To what extent regular exercise alters the liver’s adaptation to increased energy intake and what role skeletal muscle plays in this process has been studied by scientists at the Institute of Clinical Chemistry and Pathobiochemistry at the University Hospital of Tübingen and the Diabetes and Metabolic Diseases Research Institute (IDM) of Helmholtz Munich at the University of Tübingen. The researchers collaborated with the Institute for Experimental Genetics (IEG) in Helmholtz Munich, the Leibniz Institute for Analytical Sciences in Dortmund and the Institute for Chemical Physics in Dalian in China.

Exercise can prevent fatty liver disease caused by overeating

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

The results showed that training regulated important enzymes in the breakdown of glucose and fructose in the liver as well as the mitochondrial metabolism of pyruvate. 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 specific lipids such as diacylglycerol species are lowered. In addition, glucose control improves in exercise-trained mice. In addition, increased respiratory capacity of skeletal muscles relieves metabolic stress in the liver.

Systems biology data provides comprehensive insight into the molecular adaptation of liver and muscle to an energy-rich diet, training, and combinatorial effects. “The results align very well with approaches in ongoing clinical studies in which inhibitors are tested against some of the targets found here, such as the mitochondrial pyruvate transporter,” said DZD scientist Prof. Cora Weigert, head of the study and professor of molecular diabetology at the University Hospital of Tübingen. “They also show that regular physical activity regulates many targets at key metabolic pathway nodes at the same time, an effect that cannot be achieved with monotherapy.”

* Mitochondria

The task of the mitochondria is to make energy available to the cell, which occurs through cellular respiration. This is a metabolic process in which the energy stored in glucose and other organic substances is obtained by breaking the chemical bond, ultimately producing adenosine triphosphate, or ATP. It is the most important energy molecule in the body. Mitochondria are therefore also considered to be the powerhouses of the cell.

Reference: “Exercise prevents fatty liver disease by altering the compensatory response of mitochondrial metabolism to excess 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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