Lipotoxicity as the Leading Cause of Non-Alcoholic Steatohepatitis

被引:43
作者
Brankovic, Marija [1 ,2 ]
Jovanovic, Igor [1 ]
Dukic, Marija [1 ]
Radonjic, Tijana [1 ]
Opric, Svetlana [1 ]
Klasnja, Slobodan [1 ]
Zdravkovic, Marija [1 ,2 ]
机构
[1] Univ Hosp Med Ctr Bezanijska Kosa, Dr Zorza Matea Bb, Belgrade 11000, Serbia
[2] Univ Belgrade, Fac Med, Belgrade 11000, Serbia
关键词
lipids; metabolism; NASH; NAFLD; liver; FATTY LIVER-DISEASE; ENDOPLASMIC-RETICULUM STRESS; IMPROVES HEPATIC STEATOSIS; UNFOLDED PROTEIN RESPONSE; LIFE-STYLE INTERVENTIONS; INSULIN-RESISTANCE; GUT MICROBIOTA; CELL-DEATH; CARDIOVASCULAR-DISEASE; TRIGLYCERIDE SYNTHESIS;
D O I
10.3390/ijms23095146
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The emerging issues nowadays are non-alcoholic fatty liver disease (NAFLD) and its advanced stage non-alcoholic steatohepatitis (NASH), which further can be a predisposing factor for chronic liver complications, such as cirrhosis and/or development of hepatocellular carcinoma (HCC). Liver lipotoxicity can influence the accumulation of reactive oxygen species (ROS), so oxidative stress is also crucial for the progression of NASH. Moreover, NASH is in strong connection with metabolic disorders, and supporting evidence shows that insulin resistance (IR) is in a close relation to NAFLD, as it is involved in the progression to NASH and further progression to hepatic fibrosis. The major issue is that, at the moment, NASH treatment is based on lifestyle changes only due to the fact that no approved therapeutic options are available. The development of new therapeutic strategies should be conducted towards the potential NAFLD and NASH treatment by the modulation of IR but also by dietary antioxidants. As it seems, NASH is going to be the leading indication for liver transplantation as a consequence of increased disease prevalence and the lack of approved treatment; thus, an effective solution is needed as soon as possible.
引用
收藏
页数:19
相关论文
共 166 条
[71]   Non-alcoholic fatty liver disease, a new and growing risk indicator for cardiovascular disease [J].
Janssen, Arne ;
Grobbee, Diederick E. ;
Dendale, Paul .
EUROPEAN JOURNAL OF PREVENTIVE CARDIOLOGY, 2020, 27 (10) :1059-1063
[72]   Gut Microbiota-Derived Components and Metabolites in the Progression of Non-Alcoholic Fatty Liver Disease (NAFLD) [J].
Ji, Yun ;
Yin, Yue ;
Li, Ziru ;
Zhang, Weizhen .
NUTRIENTS, 2019, 11 (08)
[73]   Empagliflozin Effectively Lowers Liver Fat Content in Well-Controlled Type 2 Diabetes: A Randomized, Double-Blind, Phase 4, Placebo-Controlled Trial [J].
Kahl, Sabine ;
Gancheva, Sofiya ;
Strassburger, Klaus ;
Herder, Christian ;
Machann, Juergen ;
Katsuyama, Hisayuki ;
Kabisch, Stefan ;
Henkel, Elena ;
Kopf, Stefan ;
Lagerpusch, Merit ;
Kantartzis, Konstantinos ;
Kupriyanova, Yuliya ;
Markgraf, Daniel ;
van Gemert, Theresa ;
Knebel, Birgit ;
Wolkersdorfer, Martin F. ;
Kuss, Oliver ;
Hwang, Jong-Hee ;
Bornstein, Stefan R. ;
Kasperk, Christian ;
Stefan, Norbert ;
Pfeiffer, Andreas ;
Birkenfeld, Andreas L. ;
Roden, Michael .
DIABETES CARE, 2020, 43 (02) :298-305
[74]   Non-Alcoholic Fatty Liver Disease as a Predictor of Atrial Fibrillation in Middle-Aged Population (OPERA Study) [J].
Karajamaki, Aki J. ;
Patsi, Olli-Pekka ;
Savolainen, Markku ;
Kesaniemi, Y. Antero ;
Huikuri, Heikki ;
Ukkola, Olavi .
PLOS ONE, 2015, 10 (11)
[75]   NAFLD and cardiovascular diseases: a clinical review [J].
Kasper, Philipp ;
Martin, Anna ;
Lang, Sonja ;
Kuetting, Fabian ;
Goeser, Tobias ;
Demir, Muenevver ;
Steffen, Hans-Michael .
CLINICAL RESEARCH IN CARDIOLOGY, 2021, 110 (07) :921-937
[76]   Orchestrating the unfolded protein response in health and disease [J].
Kaufman, RJ .
JOURNAL OF CLINICAL INVESTIGATION, 2002, 110 (10) :1389-1398
[77]   Mechanisms of hepatic triglyceride accumulation in non-alcoholic fatty liver disease [J].
Kawano, Yuki ;
Cohen, David E. .
JOURNAL OF GASTROENTEROLOGY, 2013, 48 (04) :434-441
[78]   Exercise and non-alcoholic fatty liver disease: A systematic review and meta-analysis [J].
Keating, Shelley E. ;
Hackett, Daniel A. ;
George, Jacob ;
Johnson, Nathan A. .
JOURNAL OF HEPATOLOGY, 2012, 57 (01) :157-166
[79]   Modulation of Insulin Resistance in Nonalcoholic Fatty Liver Disease [J].
Khan, Reenam S. ;
Bril, Fernando ;
Cusi, Kenneth ;
Newsome, Philip N. .
HEPATOLOGY, 2019, 70 (02) :711-724
[80]   Association of Histologic Disease Activity With Progression of Nonalcoholic Fatty Liver Disease [J].
Kleiner, David E. ;
Brunt, Elizabeth M. ;
Wilson, Laura A. ;
Behling, Cynthia ;
Guy, Cynthia ;
Contos, Melissa ;
Cummings, Oscar ;
Yeh, Matthew ;
Gill, Ryan ;
Chalasani, Naga ;
Neuschwander-Tetri, Brent A. ;
Diehl, Anna Mae ;
Dasarathy, Srinivasan ;
Terrault, Norah ;
Kowdley, Kris ;
Loomba, Rohit ;
Belt, Patricia ;
Tonascia, James ;
Lavine, Joel E. ;
Sanyal, Arun J. ;
Allende, Daniela ;
Bellar, Annette ;
Dasarathy, Jaividhya ;
McCullough, Arthur J. ;
Penumatsa, Revathi ;
Reen, Jaspreet S. ;
Abdelmalek, Manal F. ;
Bashir, Mustafa ;
Buie, Stephanie ;
Kigongo, Christopher ;
Kopping, Mariko ;
Piercy, Dawn ;
Tawadrous, Naglaa ;
Cummings, Oscar W. ;
Gawrieh, Samer ;
Ragozzino, Linda ;
Rank, Dawn ;
Samala, Niharika ;
Vuppalanchi, Raj ;
Cattoor, Theresa ;
Carpenter, Danielle ;
Freebersyser, Janet ;
King, Debra ;
Lai, Jinping ;
Siegner, Joan ;
Stewart, Susan ;
Torretta, Susan ;
Wriston, Kristina ;
Gonzalez, Maria Cardona ;
Davila, Jodie .
JAMA NETWORK OPEN, 2019, 2 (10) :E1912565