| First Author | Shmarakov IO | Year | 2019 |
| Journal | Biochim Biophys Acta Mol Cell Biol Lipids | Volume | 1864 |
| Issue | 5 | Pages | 629-642 |
| PubMed ID | 30735856 | Mgi Jnum | J:274362 |
| Mgi Id | MGI:6294851 | Doi | 10.1016/j.bbalip.2019.02.004 |
| Citation | Shmarakov IO, et al. (2019) Hepatic stellate cell activation: A source for bioactive lipids. Biochim Biophys Acta Mol Cell Biol Lipids 1864(5):629-642 |
| abstractText | Hepatic stellate cells (HSCs) are non-parenchymal liver cells that characteristically contain multiple retinoid (vitamin A)-containing lipid droplets. In this study, we addressed the metabolic fate of non-retinoid lipids originating from lipid droplet loss during HSCs activation. UPLC/MS/MS and qRT-PCR were used to monitor the lipid composition and mRNA expression of selected genes regulating lipid metabolism in freshly isolated, overnight-, 3- and 7-day cultures or primary mouse HSCs. A preferential accumulation of specific C20-C24 fatty acid species, especially arachidonic (C20:4) and docosahexaenoic acids (C22:6), was revealed in culture-activated HSCs along with an upregulation of transcription of fatty acid desaturases (Scd1, Scd2) and elongases (Elovl5, Elovl6). This was accompanied with an enrichment of activated HSCs with 36:4 and 38:4 phosphatidylcholine species containing polyunsaturated fatty acids and associated accumulation of selective lipid mediators, including endocannabinoids and related N-acylethanolamides, as well as ceramides. An increase in 2-arachidonoylglycerol and N-arachydonoylethanolamide concentrations was observed along with an upregulation of Daglalpha mRNA expression in HSCs during culture activation. N-palmitoylethanolamide was identified as the most abundant endocannabinoid-like species in activated HSCs. An increase in total ceramide levels and enrichment with N-palmitoyl (C16:0), N-tetracosenoyl (C24:1), N-tetracosanoyl (C24:0) and N-docosanoyl (C22:0) ceramides was detected in activated HSC cultures and was preceded by increased mRNA expression of ceramide synthesizing enzymes (CerS2, CerS5 and Smpd1). Our data suggest an active redistribution of non-retinoid lipids in HSCs underlying the formation of low abundance, highly bioactive lipid species that may affect signaling during HSC activation, as well as extracellularly within the liver. |
