Mushrooms on the plate: Trends towards NAFLD treatment, health improvement and sustainable diets.

Non-alcoholic fatty liver disease (NAFLD) is a most important cause of liver disease. Similar to other non-communicable diseases (NCD), such as obesity and type II diabetes mellitus, NAFLD can strongly affected by diet. Diet-related NCD and malnutrition are rising in all regions being a major cause of the global health, economic and environmental burdens. Mushrooms, important dietary components since the hunter-gathering communities, have increasingly gained momentum in biomedical research and therapeutics due to their interplay in metabolism traits. We emphasize here the beneficial effects of mushroom-enriched diets on the homeostasis of lipid and sugar metabolism, including their modulation, but also interfering with insulin metabolism, gut microbiota, inflammation, oxidative stress and autophagy. In this review, we describe the cellular and molecular mechanisms at the gut-liver axis and the liver-white adipose tissue (WAT) axis, that plausibly cause such positive modulation, and discuss the potential of mushroom-enriched diets to prevent or ameliorate NAFLD and related NCD, also within the shift needed towards healthy sustainable diets.

Antioxidant Versus Pro-Apoptotic Effects of Mushroom-Enriched Diets on Mitochondria in Liver Disease.

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.