Shedding light on non-alcoholic fatty liver disease: Pathogenesis, molecular mechanisms, models, and emerging therapeutics

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder globally impacting an estimated 25% of the population associated with severe consequences such as cirrhosis, hepatocellular carcinoma (HCC), and overall mortality. Fatty liver disease is triggered through multiple pat...

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Bibliographic Details
Published in:Life sciences (1973) 2023-01, Vol.312, p.121185-121185, Article 121185
Main Authors: Khairnar, Rhema, Islam, Md Asrarul, Fleishman, Joshua, Kumar, Sunil
Format: Article
Language:English
Subjects:
Carcinoma, Hepatocellular - pathology
Emerging therapeutics
Hepatic lipid metabolism
Humans
Liver - metabolism
Liver Cirrhosis - pathology
Liver Neoplasms - pathology
NAFLD
Non-alcoholic Fatty Liver Disease - metabolism
Pathogenesis
Pre-clinical models
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Summary:Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disorder globally impacting an estimated 25% of the population associated with severe consequences such as cirrhosis, hepatocellular carcinoma (HCC), and overall mortality. Fatty liver disease is triggered through multiple pathways, but the most prominent cause is either diabetes or obesity, or a combination of both. Therefore, hepatic glucose, insulin and fatty acid signaling becomes a dire need to understand which is well elaborated in this review. This review summarizes the popular two-hit pathogenesis of NAFLD, the molecular mechanisms underlying hepatic insulin resistance. As fatty liver disease gets advanced, it requires in-vitro as well as in-vivo models closer to disease progression in humans for better understanding the pathological state and identifying a novel therapeutic target. This review summarizes in-vitro (2D cell-culture/co-culture, 3D spheroid/organoid/liver-on-a-chip) models as well as in-vivo (genetically/dietary/chemically induced fatty liver disease) research models. Fatty liver disease research has gathered lots of attention recently since there is no FDA approved therapy available so far. However, there have been numerous promising targets to treat fatty liver disease including potential therapeutic targets under clinical trials are listed in this review. [Display omitted]
ISSN:0024-3205
1879-0631
DOI:10.1016/j.lfs.2022.121185