Abstract
Mitochondria play a central role in non-alcoholic fatty liver disease (NAFLD) progression and in the control of cell death signalling during the progression to hepatocellular carcinoma (HCC). Associated with the metabolic syndrome, NAFLD is mostly driven by insulin-resistant white adipose tissue lipolysis that results in an increased hepatic fatty acid influx and the ectopic accumulation of fat in the liver. Upregulation of beta-oxidation as one compensatory mechanism leads to an increase in mitochondrial tricarboxylic acid cycle flux and ATP generation. The progression of NAFLD is associated with alterations in the mitochondrial molecular composition and respiratory capacity, which increases their vulnerability to different stressors, including calcium and pro-inflammatory molecules, which result in an increased generation of reactive oxygen species (ROS) that, altogether, may ultimately lead to mitochondrial dysfunction. This may activate further pro-inflammatory pathways involved in the progression from steatosis to steatohepatitis (NASH). Mushroom-enriched diets, or the administration of their isolated bioactive compounds, have been shown to display beneficial effects on insulin resistance, hepatic steatosis, oxidative stress, and inflammation by regulating nutrient uptake and lipid metabolism as well as modulating the antioxidant activity of the cell. In addition, the gut microbiota has also been described to be modulated by mushroom bioactive molecules, with implications in reducing liver inflammation during NAFLD progression. Dietary mushroom extracts have been reported to have anti-tumorigenic properties and to induce cell-death via the mitochondrial apoptosis pathway. This calls for particular attention to the potential therapeutic properties of these natural compounds which may push the development of novel pharmacological options to treat NASH and HCC. We here review the diverse effects of mushroom-enriched diets in liver disease, emphasizing those effects that are dependent on mitochondria.
Highlights
Non-Alcoholic Fatty Liver Disease (NAFLD) is a metabolic condition characterized by the accumulation of fat in more than 5% of the liver parenchyma, which is observed in the absence of other recognized causes of fatty liver
NAFLD can progress from isolated macro- or microvesicular steatosis (NAFL) to non-alcoholic steatohepatitis (NASH), a pathological state characterized by steatosis, inflammation and hepatocellular ballooning [2]
NASH increases the risk for hepatocellular carcinoma (HCC), even independently of cirrhosis, and whilst cardiovascular diseases (CVDs) represent the main cause of death in NAFLD patients, an increase in liver-related mortality is expected in upcoming years
Summary
Non-Alcoholic Fatty Liver Disease (NAFLD) is a metabolic condition characterized by the accumulation of fat in more than 5% of the liver parenchyma, which is observed in the absence of other recognized causes of fatty liver (alcohol, chronic viral infection, drugs, autoimmunity, etc.) [1]. Mushrooms are a rich source of bioactive compounds known for their modulatory activities on the gut microbiota and enteric absorption, their antioxidant activity and their pro-apoptotic action [20,21,22,23,24,25] These pleiotropic effects on metabolism and their influence on mitochondrial function might call upon mushroom compounds as interesting candidates for NASH and HCC therapeutics. Mushrooms and truffles are an excellent source of polysaccharides (α/ß-D-glucans) [27], proteins [28,29], vitamins (B1, B2, B12, C, D, and E), minerals, and essential amino acids; they are low in total fat but have a high content of polyunsaturated fatty acids They are rich in phenolic acids, such as hydroxybenzoic and hydroxycinnamic acid, flavonoids, tocopherols, ascorbic acid and carotenoids that are known for their antioxidant activity [24,30,31]. Associated to cultural heritage, fungi are known for their common name, which for the purposes of this review are mentioned between brackets following the scientific name
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