Aging Mitochondrial Function May Increase Risk of Diet-induced Fatty Liver Disease

Özge Özkaya, PhD avatar

by Özge Özkaya, PhD |

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Age indirectly influences mitochondrial function by reducing mitochondrial mass and worsens diet‐induced fat accumulation, according to a study conducted on mice. This may in turn increase the risk of developing non-alcoholic fatty liver disease (NAFLD).

Mitochondria are the energy factories of the cells. They metabolize fatty acids to generate this energy. However, with their mass and function declining with age, they cannot deal with the large amount of fatty acids associated with a high-fat diet.

A team of researchers led by Dr. Martin Klingenspor of Technische Universität München in Munich, Germany, addressed the effect of a high-fat diet and age on liver mitochondria at an early stage of NAFLD development.

They analyzed the functional characteristics of liver mitochondria and associated changes in the mitochondrial function in response to a high-fat diet in adolescent, young adult, and middle‐aged mice.

When fed a high-fat diet, young adult and middle‐aged mice developed a fatty liver, whereas adolescent mice did not. They also found that susceptibility to diet‐induced obesity increased with age, suggesting that this may be linked to a reduction in the mass of mitochondria and their capacity to oxidize fatty acids.

The researchers also found that, regardless of age, a high-fat diet increased the production of reactive oxygen species (ROS), which are considered to be critical in the development of fatty liver disease.

When they conducted a large-scale analysis of proteins expression, the researchers discovered that a protein called NFE2L2 was induced in the liver of these mice. NFE2L2 may play a role as a key regulator of the anti-oxidative response to high-fat diet induced mitochondrial ROS production in liver.

NAFLD is the most common form of chronic liver disease in the U.S., with around 80 million to 100 million people affected, and a major health burden in the aging society with an urgent medical need.

According to the researchers, the effects of aging on metabolism must be taken into account in order to clarify the underlying mechanism of NAFLD.

The study, “Reduced mitochondrial mass and function add to age‐related susceptibility toward diet‐induced fatty liver in C57BL/6J mice,” was published in the journal Physiological Reports.