Comparison of Lipidomics Profiles of Patients with Nonalcoholic Steatohepatitis to an In Vitro-Induced Steatosis Sandwich Cultured Hepatocyte Model | Dr. Thomas Kralj

Nonalcoholic steatohepatitis (NASH) is a severe form of steatotic liver injury with multifactorial etiologies, and a significant mortality rate. A common technique to study in vitro steatosis involves culturing primary human hepatocytes (PHH) in a fatty acid-enriched media. We conducted a study to compare the lipidome of PHH cultured in a fatty acid-enriched media to hepatocytes from patients with NASH and healthy controls to determine whether such culture techniques could generate a hepatocellular lipid profile similar to that observed in NASH patients. LC-MS lipidomics analysis of hepatocytes from patients with NASH revealed increases in the total cellular abundance of glycerolipids, phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerols, phosphatidylinositols and phosphatidylserines compared to healthy control hepatocytes. PHH cultured in a fatty acid-enriched environment demonstrated an increase in total lipid abundance, however, changes were limited to glycerolipids.  In contrast to NASH hepatocytes, increases in the abundance of phospholipids were not observed. The changes to specific lipid classes are often overlooked in favor of achieving increased total lipids and histological changes consistent with the clinical presentation of NASH, however, due to the complex nature of lipid interactions and regulation a more complete lipidome may better recapitulate clinical steatosis.  It is vital to understand the limitations and assumptions of in vitro models used to stimulate in vivo behavior.

This webinar is sponsored by BioIVT.