How regular exercise can protect against fatty liver associated diseases

Worldwide one in four persons suffers from non-alcoholic liver disease (NAFLD, also called metabolic liver disease MAFLD). Those affected often have type 2 diabetes as well as an increased risk of liver cirrhosis and cardiovascular diseases. In addition, NAFLD is associated with increased mortality. An imbalance between energy intake and consumption is discussed as a cause for 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.

The results showed that training regulated important enzymes of glucose and fructose degradation in the liver as well as the mitochondrial pyruvate metabolism. In this way, the substrate burden for mitochondrial respiration and lipid synthesis can be reduced. As a consequence, less fat is stored in the liver – and specific lipids such as diacylglycerol species are lowered. Moreover, glucose control improves in the exercise trained mice. In addition, an increased respiratory capacity of the skeletal muscles relieves the metabolic stress 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 in 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," said DZD scientist Prof. Dr. Cora Weigert, head of the study and professor of molecular diabetology at Tübingen University Hospital. "They also show that regular physical activity regulates many targets at the same time key nodes of metabolic pathways, an effect that cannot be achieved with monotherapy."