Abstract
In contrast to nonalcoholic fatty liver disease (NAFLD), metabolic-associated fatty liver disease (MAFLD) as an innovative definition can coexist with significant alcohol consumption. Massive clinical observations have indicated that high-fat/-calorie diet induced metabolic dysfunction along with alcohol intake deteriorates steatotic liver injury. To explore the potential mechanisms of fatty diet together with alcohol-induced steatohepatitis, we adopted a rat model by comparing a half-dose combination of fat diet (20%) and alcohol (10%) with their corresponding double dose of 40% fat diet and 20% alcohol for 8 weeks. The notable alterations in histopathology, acceleration in the oxidation parameters (ROS, NO and lipid peroxidation) and serum transaminase levels were shown in the concomitant group. Concomitant use of a high-fat diet and alcohol provoked hepatic endoplasmic reticulum stress, but did not activate mitochondria-mediated apoptosis parameters compared to F. In contrast, the notable activation of caspase-12 and nuclear translocation of CCAAT/enhancer-binding protein (C/EBP) homologous protein (CHOP) were observed only in the combined treatment group. The concomitant dietary fat intake and alcohol consumption lead to liver injury initially and later to steatohepatitis by the overdose of fat or alcohol, and in which the CHOP and caspase-12 might be involved in synergistic acceleration of steatohepatitis through a mitochondria-independent manner.
Highlights
The decreased carrier of hepatic viruses and an increase in the population suffering from obesity lead to high-fat diets and alcohol abuse becoming major causes of liver diseases, especially in industrialized countries [1,2]
The body weights and visceral fat weights were significantly increased in the fat diet 40 and fat diet 20 groups followed by the combined treatment group and the ethanol 20 and ethanol 10 group (Table 1), whereas the liver tissue weights and hepatic lipid contents (TC and TG) were significantly increased in the combined treatment group compared with the high-fat diet groups or alcohol consumption groups (p < 0.05, Table 1, Figure 1I,J)
The serum levels of total total cholesterol (TC), low-density lipoprotein (LDL), TG, glucose and free fatty acid were significantly higher in the combined treatment group compared to other groups (p < 0.05 or 0.01, Table 1)
Summary
The decreased carrier of hepatic viruses and an increase in the population suffering from obesity lead to high-fat diets and alcohol abuse becoming major causes of liver diseases, especially in industrialized countries [1,2]. NASH and ASH have a different etiology depending on the clinical diagnostic criteria, such as the amount of alcohol consumption (generally 20 g/day for women and 30 g/day for men) [7]. Their pathological features and histopathological characteristics are too similar, almost indistinguishable in terms of excessive fat accumulation and cellular damage [8]. They are both provoked by a complex process involving the imbalance between lipogenesis and lipolysis, as well as an increase of the imported fat to the liver, followed by harmful events, including an inflammatory response [9,10]. Metabolic-associated fatty liver disease (MAFLD) is increasingly recognized as the more appropriate nomenclature than non-alcoholic fatty liver disease (NAFLD) owing to better interpretation of heterogeneous pathogenesis, including co-existence with alcoholic consumption and other inducers [14]
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