Mitochondrial Dysfunction in Metabolic Dysfunction Fatty Liver Disease (MAFLD)

Abstract

Nonalcoholic fatty liver disease (NAFLD) has become an increasingly common disease in Western countries and has become the major cause of liver cirrhosis or hepatocellular carcinoma (HCC) in addition to viral hepatitis in recent decades. Furthermore, studies have shown that NAFLD is inextricably linked to the development of extrahepatic diseases. However, there is currently no effective treatment to cure NAFLD. In addition, in 2020, NAFLD was renamed metabolic dysfunction fatty liver disease (MAFLD) to show that its pathogenesis is closely related to metabolic disorders. Recent studies have reported that the development of MAFLD is inextricably associated with mitochondrial dysfunction in hepatocytes and hepatic stellate cells (HSCs). Simultaneously, mitochondrial stress caused by structural and functional disorders stimulates the occurrence and accumulation of fat and lipo-toxicity in hepatocytes and HSCs. In addition, the interaction between mitochondrial dysfunction and the liver–gut axis has also become a new point during the development of MAFLD. In this review, we summarize the effects of several potential treatment strategies for MAFLD, including antioxidants, reagents, and intestinal microorganisms and metabolites.

Can Nutraceuticals Support the Treatment of MASLD/MASH, and thus Affect the Process of Liver Fibrosis?

“…The analysis of data from the National Health and Nutrition Examination Survey (NHANES) showed a relationship between serum vitamin C concentration and a lower risk of developing liver fibrosis in men and overweight or obese patients with MASLD [97]. The previous analysis of NHNES data provided similar evidence.…”

Underlying Mechanisms behind the Brain–Gut–Liver Axis and Metabolic-Associated Fatty Liver Disease (MAFLD): An Update

“…Consequently, as mitochondrial function declines, the oxidative impact of metabolic reactions intensifies, leading to increased production of reactive species and damage to mitochondrial constituents, including membranes, proteins, and genetic material. In response to oxidative stress, mitochondria initiate their quality control mechanisms (MQC) to preserve their architecture and genetic integrity, thereby impeding the progression of MAFLD [78,79]. The interplay between endoplasmic reticulum stress (ERS) and oxidative stress significantly contributes to the pathogenesis of this condition [80].…”

Early monitoring values of oncogenic signalling molecules for hepatocellular carcinoma

“…The prevention, early monitoring or diagnosis of hepatocellular carcinoma (HCC) are still urgent medical problems[ 1 , 2 ]. Hepatocarcinogenesis is mainly related to chronic persistent hepatitis virus infection [hepatitis B virus (HBV), hepatitis C virus (HCV) or hepatitis D virus][ 3 , 4 ], chemical carcinogen intake, and increased metabolic dysfunction-associated fatty liver disease (MAFLD)[ 5 , 6 ]. Recently, MAFLD has become one of the most chronic liver diseases and a possible etiological factor for liver cancer[ 7 , 8 ].…”