9-POHSA prevents NF-kB activation and ameliorates LPS-induced inflammation in rat hepatocytes

Lipids. 2023 Sep;58(5):241-249. doi: 10.1002/lipd.12380. Epub 2023 Aug 21.

Abstract

Liver inflammation has become increasingly prevalent in recent years, leading to the development of diseases like hepatitis, alcoholic liver disease, and fatty liver disease. One factor that has been linked to liver inflammation is increased levels of lipopolysaccharides (LPS), which can be caused by poor diets and sedentary lifestyles that contribute to liver inflammation. There is promising research on a new class of lipids called fatty acid esters of hydroxy fatty acids (FAHFAs), which have been shown to potentiate insulin release and exert an anti-inflammatory effect. Specifically, one type of FAHFA called 9-POHSA (palmitoleic acid ester of 9-hydroxy stearic acid) has been studied for its potential to attenuate inflammation-related indexes induced by LPS in hepatocytes, which play a critical role in the progression of liver inflammation. This study found that following LPS treatment, tumor necrosis factor- α, interleukin-6, and connective tissue growth factor (CTGF) were upregulated and increased cell migration, but 9-POHSA pre-treatment attenuated the upregulation of these markers and prevented cell migration induced by LPS. Using flowcytometry analysis, intracellular reactive oxygen species (ROS) was found to be responsible for CTGF upregulation. In addition, the effects of 9-POHSA were likely associated with its inhibition of the activation of the NF-kB. These results suggest that 9-POHSA has potential as a therapy for liver inflammation and fibrosis by attenuating inflammation-related indexes induced by LPS in hepatocytes. This study provides important insight into the mechanisms of liver inflammation and the potential for new treatments to address liver diseases.

Keywords: 9-POHSA; FAHFA; LPS; fatty liver; hepatocyte; liver inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Movement
  • Fatty Acids
  • Hepatocytes
  • Hydroxy Acids
  • Inflammation / chemically induced
  • Inflammation / drug therapy
  • Lipopolysaccharides* / toxicity
  • NF-kappa B*
  • Rats

Substances

  • Lipopolysaccharides
  • NF-kappa B
  • Fatty Acids
  • Hydroxy Acids