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According to a study done with animal models and published in the journal Metabolism, aerobic exercise could help fight against fatty liver disease not associated with alcohol consumption, the most common liver pathology in the world that affects about 24% of people. the world's population and often causes a certain stigma among affected people. The work opens new avenues to identify this process in patients and, thus, design new strategies to prevent the progression of the pathology.
The article is directed by Professor María Isabel Hernández-Álvarez, from the Faculty of Biology of the University of Barcelona, the Institute of Biomedicine (IBUB) and the Center for Biomedical Research in the Network of Diabetes and Associated Metabolic Diseases (CIBERDEM), in collaboration with Rodrigo Troncoso, from the Universidad de Chile, and Víctor Cortés, from the Pontificia Universidad Católica de Chile.
When the liver accumulates large amounts of fat
One of the characteristics of fatty liver disease or nonalcoholic steatohepatitis (NAFLD) is the high concentration of lipid droplets (LD) that accumulate in liver cells. "Our findings reveal that aerobic exercise, that is, moderate physical activity over time, helps metabolize fat because it reduces the amount of lipid droplets and, therefore, the severity of the disease," notes the author.
“Thus, then, the energy demands induced by exercise determine regulated changes in the physical and functional relationships between fat droplets and mitochondria, the cellular organelles that provide energy for metabolism,” adds Hernández-Álvarez.
This interaction would take place in a specific population of mitochondria known as peridot mitochondria. “As a result, there is increased oxidation of lipids in this specific population of mitochondria, a process that helps prevent the progression of pathology.”
Discovering a previously unknown connection
“The interaction between lipid droplets and mitochondria is functionally important for the homeostasis of fat metabolism. Exercise improves fatty liver disease, but until now it was not known if the disease had a direct effect on the interactions between hepatic LDs and mitochondria," explains María Isabel Hernández-Álvarez, who is a Ramón y Cajal prostdoctoral researcher at the Department of Biochemistry and Molecular Biomedicine of the UB.
The work also highlights that mitofusin 2 (Mfn2) – a protein that is located in the outer membrane of mitochondria – has a decisive role in this process, since it modifies the communication between lipid droplets and the specific population of mitochondria.
“In the study, we found a decrease in the relative content of saturated fatty acids in the liver mitochondrial membranes of animals that had exercised. This suggests to us that the fluidity of the membrane increases in these mitochondria,” indicates the researcher. “In the case of mice without the Mfn2 gene and exposed during physical activity, no changes are observed in the saturation and metabolism of fatty acids. "These results indicate that the Mfn2 protein participates in the regulation of the fatty acid composition of mitochondrial membranes in response to exercise."
According to the authors, the Mfn2 protein would regulate the curvature of the mitochondrial membrane and promote fat oxidation in a population of mitochondria, through its interaction and ability to form specific domains with membrane phospholipids.
The new work is a step forward to enhance research on molecular mediators and mechanisms that could drive new strategies to prevent the progression of NAFLD. “Taking into account the functions of Mfn2 in mitochondrial morphology and the liver, therapeutic manipulations of Mfn2 levels and activity could contribute to improving the inflammation associated with NAFLD,” concludes the researcher.
