Document Type
Article
Publication Date
5-2024
Abstract
Globally, non-alcoholic fatty liver disease (NAFLD) is on the rise with 30-32%, 27-33%, 35-48%, 36%, 9-20%, and 36-38% prevalence in Asia, Europe, North America, South America, Africa, and Australia, respectively. Approximately, 5-10% of NAFLD proceeds to hepatitis called non-alcoholic steatohepatitis (NASH). NASH often progresses to liver fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Precise mechanism(s) for the development of HCC is not fully understood in NAFLD and NASH patients. Higher insulin levels in type 2 diabetes (T2D) can result in lipolysis of adipose tissue activating lipid synthesizing enzymes such as fatty acid synthase and stearoyl-CoA desaturase-1, resulting in lipid accumulation in liver. Higher levels of glucose in T2D patients activate carbohydrate response element binding protein and insulin which increases the level of active sterol regulatory element binding protein. These lipogenic transcription factors activate patatin-like phospholipase domain-containing protein-3 (PNPLA3) from their response elements in the promoter. Endocrine disrupting chemicals (EDCs) and persistent organic pollutants (POPs) are implicated in T2D development and NAFLD. The emerging association between POPs, including insecticides, fungicides, herbicides, and diabetes has been noted. However, their connection with NAFLD remains less evident. Here, we reviewed association of POPs, especially EDCs, and role of PNPLA3 in the development of NAFLD and NASH. We also reviewed the role of single nucleotide polymorphisms of PNPLA3’s association with NAFLD.
Recommended Citation
Saghir S, Abbas A, Alfuraih S, Sharma A, Latimer J, Omidi Y, et al. Non-alcoholic fatty liver disease: Role of PNPLA3 and its association with environmental chemicals. Arch Clin Toxicol. 2024;6(1):21-32. https://doi.org/10.46439/toxicology.6.029
Copyright
The authors
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
This article was originally published in Archives of Clinical Toxicology, volume 6, issue 1, in 2024. https://doi.org/10.46439/toxicology.6.029