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Hepatic stellate cell activation: A source for bioactive lipids.

Igor O Shmarakov1, Hongfeng Jiang1, Jing Liu1

  • 1Department of Medicine, Vagelos College of Physicians and Surgeons, Columbia University, 630 West 168(th) Street, New York, NY 10032, USA.

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|February 9, 2019
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Summary

Activated hepatic stellate cells (HSCs) redistribute non-retinoid lipids, accumulating bioactive species like polyunsaturated fatty acids, endocannabinoids, and ceramides. This lipid remodeling influences HSC signaling and extracellular liver environment.

Keywords:
CeramidesEndocannabinoidsLipid dropletsLipidomicsPhosphatidylcholinePolyunsaturated fatty acids

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Area of Science:

  • Hepatology
  • Lipid Metabolism
  • Cell Biology

Background:

  • Hepatic stellate cells (HSCs) store vitamin A in lipid droplets.
  • HSC activation involves changes in lipid metabolism.
  • The fate of non-retinoid lipids during HSC activation is not fully understood.

Purpose of the Study:

  • To investigate the metabolic fate of non-retinoid lipids during HSC activation.
  • To identify specific lipid species that accumulate in activated HSCs.
  • To understand the role of lipid remodeling in HSC signaling.

Main Methods:

  • Primary mouse HSCs cultured for varying durations.
  • UPLC/MS/MS analysis for lipid composition.
  • qRT-PCR for gene expression of lipid-metabolizing enzymes.

Main Results:

  • Culture-activated HSCs showed preferential accumulation of C20-C24 fatty acids, including arachidonic and docosahexaenoic acids.
  • Upregulation of fatty acid desaturases (Scd1, Scd2) and elongases (Elovl5, Elovl6) was observed.
  • Enrichment with polyunsaturated phosphatidylcholines, endocannabinoids (e.g., N-palmitoylethanolamide), and specific ceramides occurred.
  • Increased mRNA expression of ceramide synthesizing enzymes (CerS2, CerS5, Smpd1) preceded ceramide accumulation.

Conclusions:

  • HSCs actively redistribute non-retinoid lipids during activation.
  • This process generates bioactive lipid species that may impact HSC signaling.
  • Lipid remodeling in HSCs could influence the extracellular liver environment.