Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms

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 al...

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Main Authors: Hyeong-Geug Kim, Jing-Hua Wang, Hyo-Seon Kim, Jin-Seok Lee, Hwi-Jin Im, Sung-Bae Lee, Dong-soo Lee, Gang-Min Hur, Chang-Gue Son
Format: Article
Language:English
Published: MDPI AG 2021-04-01
Series:Journal of Personalized Medicine
Subjects:
Online Access:https://www.mdpi.com/2075-4426/11/4/287
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author Hyeong-Geug Kim
Jing-Hua Wang
Hyo-Seon Kim
Jin-Seok Lee
Hwi-Jin Im
Sung-Bae Lee
Dong-soo Lee
Gang-Min Hur
Chang-Gue Son
author_facet Hyeong-Geug Kim
Jing-Hua Wang
Hyo-Seon Kim
Jin-Seok Lee
Hwi-Jin Im
Sung-Bae Lee
Dong-soo Lee
Gang-Min Hur
Chang-Gue Son
author_sort Hyeong-Geug Kim
collection DOAJ
description 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.
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spelling doaj.art-3ea024357a464df0958059146b5ee5de2023-11-21T14:45:50ZengMDPI AGJournal of Personalized Medicine2075-44262021-04-0111428710.3390/jpm11040287Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential MechanismsHyeong-Geug Kim0Jing-Hua Wang1Hyo-Seon Kim2Jin-Seok Lee3Hwi-Jin Im4Sung-Bae Lee5Dong-soo Lee6Gang-Min Hur7Chang-Gue Son8Institute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaInstitute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaInstitute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaInstitute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaInstitute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaInstitute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaDepartment of Internal Medicine, Daejeon St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 64, Daeheung-ro, Jung-gu, Daejeon 34943, KoreaDepartment of Pharmacology, Research Institute for Medical Science, College of Medicine, Chungnam National University, Daejeon 301131, KoreaInstitute of Bioscience & Integrative Medicine, Daejeon University, 75, Daedeok-daero 176, Seo-gu, Daejeon 35235, KoreaIn 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.https://www.mdpi.com/2075-4426/11/4/287steatohepatitismetabolic associated fatty liver diseasealcoholic liver diseasesendoplasmic reticulum stressmitochondriaNAFLD
spellingShingle Hyeong-Geug Kim
Jing-Hua Wang
Hyo-Seon Kim
Jin-Seok Lee
Hwi-Jin Im
Sung-Bae Lee
Dong-soo Lee
Gang-Min Hur
Chang-Gue Son
Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms
Journal of Personalized Medicine
steatohepatitis
metabolic associated fatty liver disease
alcoholic liver diseases
endoplasmic reticulum stress
mitochondria
NAFLD
title Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms
title_full Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms
title_fullStr Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms
title_full_unstemmed Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms
title_short Animal Evidence for Synergistic Induction of Hepatic Injury by Dietary Fat and Alcohol Consumption and Its Potential Mechanisms
title_sort animal evidence for synergistic induction of hepatic injury by dietary fat and alcohol consumption and its potential mechanisms
topic steatohepatitis
metabolic associated fatty liver disease
alcoholic liver diseases
endoplasmic reticulum stress
mitochondria
NAFLD
url https://www.mdpi.com/2075-4426/11/4/287
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