AI Article Synopsis

  • - Nonalcoholic steatohepatitis (NASH) is linked to obesity and type 2 diabetes, leading to a higher risk of serious liver complications like cirrhosis and cancer, and the enzyme Elovl6 plays a vital role in fat metabolism in the liver.
  • - Research using mouse models and human samples shows that Elovl6 influences liver inflammation, oxidative stress, and damage, with its expression levels tied to the severity of liver issues in NASH patients.
  • - Targeting Elovl6 might provide new therapeutic strategies for preventing and treating NASH by altering hepatic fatty acid composition.

Article Abstract

Unlabelled: Nonalcoholic steatohepatitis (NASH) is associated with obesity and type 2 diabetes, and an increased risk for liver cirrhosis and cancer. ELOVL family member 6, elongation of very long chain fatty acids (Elovl6), is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have shown previously that Elovl6 is a major target for sterol regulatory element binding proteins in the liver and that it plays a critical role in the development of obesity-induced insulin resistance by modifying FA composition. To further investigate the role of Elovl6 in the development of NASH and its underlying mechanism, we used three independent mouse models with loss or gain of function of Elovl6, and human liver samples isolated from patients with NASH. Our results demonstrate that (1) Elovl6 is a critical modulator for atherogenic high-fat diet-induced inflammation, oxidative stress, and fibrosis in the liver; (2) Elovl6 expression is positively correlated with severity of hepatosteatosis and liver injury in NASH patients; and (3) deletion of Elovl6 reduces palmitate-induced activation of the NLR family pyrin domain-containing 3 inflammasome; this could be at least one of the underlying mechanisms by which Elovl6 modulates the progress of NASH.

Conclusion: Hepatic long-chain fatty acid composition is a novel determinant in NASH development, and Elovl6 could be a potential therapeutic target for the prevention and treatment of NASH.

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http://dx.doi.org/10.1002/hep.25932DOI Listing

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  • - ELOVL6 is an important enzyme involved in lipid metabolism, specifically elongating fatty acids with carbon chains of C12-C16, and is linked to conditions like insulin resistance, non-alcoholic fatty liver disease, and cardiovascular diseases.
  • - Recent studies suggest that ELOVL6 also connects to kidney diseases, neurological disorders such as epilepsy, and pulmonary fibrosis, with its expression influenced by factors like diet and oxidative stress.
  • - As a potential target for diagnosis and therapy, ongoing research aims to explore ELOVL6's mechanisms in disease, which could lead to new treatment approaches for various health issues.
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