Cellular Metabolism and NAFLD/NASH
Nonalcoholic fatty liver disease (NAFLD) is a pathological change in the liver that occurs predominantly in the elderly, regardless of drinking history. NAFLD is a comprehensive disease concept that progresses from fatty liver (steatosis) through nonalcoholic steatohepatitis (NASH) to fibrosis/cirrhosis and finally hepatocellular carcinoma (HCC).
Recently, it has been reported that cellular senescence and associated mitochondrial dysfunctions contribute significantly to the development of NAFLD/NASH, and these reports have attracted much attention.
Obesity, a risk factor for NAFLD/NASH, increases lipid deposition, which then promotes the production of reactive oxygen species (ROS) and inflammatory cytokines, leading to cellular senescence. The decrease in NAD+ levels associated with cellular senescence results in a decrease in mitochondrial function. The decrease in mitochondrial function then leads to a further decrease in NAD+ levels, which exacerbates senescence-like changes in cellular function.
On the other hand, liver-specific induction of cellular senescence has been shown to increase lipid deposition and promote fibrosis. This indicates that cellular senescence, abnormal mitochondrial function, and associated metabolic changes produce a synergy in the development of NAFLD/NASH, forming inflammatory and fibrotic pathologies.
In the future, more detailed analysis of the relationship between this complex synergy and NAFLD/NASH is expected to contribute to the establishment of new treatments.
Reported cases in each NAFLD/NASH model
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