BARCELONA, Spain — The most common liver disease on the planet, non-alcoholic fatty liver disease (NAFLD) affects close to one in four individuals on a global scale. This unhealthy buildup of fat in the liver is common among overweight or obese patients. As obesity rates continue to rise worldwide, more and more people all over are developing NAFLD. Now, however, a new study examining animals finds aerobic exercise may help treat NAFLD.
Professor María Isabel Heràndez-Alvarez of the University of Barcelona put this study together, in collaboration with Rodrigo Troncoso from the University of Chile and Víctor Cortés from the Pontifical Catholic University of Chile. Overall, researchers say this work provides new possibilities for both identifying the progression of NAFLD in patients and designing new strategies to prevent its development.
One of the key features of non-alcoholic fatty liver disease is the large concentration of lipid droplets (LD) that build up within the liver cells.
“Our findings reveal that aerobic exercise, that is, moderate physical activity over time, helps metabolize the fats because it reduces the size of lipid droplets, and therefore, the severity of the disease,” notes Professor María Isabel Heràndez-Alvarez, from the Faculty of Biology of the University of Barcelona, the Institute of Biomedicine (IBUB) and the Diabetes and Associated Metabolic Diseases Networking Biomedical Research Centre (CIBERDEM), in a media release.
“Therefore, the energy demands induced by the exercise determine regulated changes in physical and functional relationships between fat droplets and mitochondria, the cell organelles that provide energy for the metabolism.”
This interaction may take place among a specific population of mitochondria called peridroplet mitochondria (PDM).
“As a result, there is a higher oxidation of lipids in this specific population of mitochondria, a process that helps prevent the progress of the disease,” Prof. Heràndez-Alvarez continues.
“The interaction between the lipid droplets (LD) and the mitochondria is functionally important for the homeostasis of the fat metabolism. Exercise improves fatty liver disease, but to date, it was unknown whether the disease had a direct impact on the interactions between hepatic LDs and mitochondria,” explains Prof. Hernàndez-Alvarez, Ramón y Cajal postdoctoral researcher at the UB’s Department of Biochemistry and Molecular Biomedicine.
Study authors stress that mitofusin 2 (Mfn-2), which is a protein found in the external membrane of mitochondria, appears to play a decisive role in this process. The protein modifies communications between lipid droplets and the specific mitochondria population.
“We found a decrease in the content related to saturated fatty acids in the hepatic mitochondrial membranes of animals that had done physical activity. This suggests that membrane fluidity increases in the mitochondria,” Prof. Heràndez-Alvarez explains. “In the case of the mice without the Mfn-2 gene, exposed to physical activity, we did not observe changes in the saturation and the metabolism of fatty acids. These results show that the Mfn-2 protein takes part in the regulation of the composition of fatty acids of the mitochondrial membranes in response to exercise.”
Researchers explain that the Mfn-2 protein regulates the curve of the mitochondrial membrane while promoting fat oxidation in specific mitochondria populations. This happens via its interaction and ability to form specific domains with membrane phospholipids. In summation, this work represents a major step forward when it comes to understanding mediators and molecular mechanisms that may promote new strategies in the prevention of NAFLD.
“Considering the Mfn-2 functions in mitochondrial morphology and in the liver, the therapeutic manipulations of the levels and the activity of Mfn-2 could contribute to the improvement of the NAFLD-related inflammation and the fibrosis,” Prof. Heràndez-Alvarez concludes.
The study is published in the journal Metabolism.