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Hormone-sensitive lipase is a retinyl ester hydrolase in human and rat quiescent hepatic stellate cells

Shajari, S., Saeed, A., Smith-Cortinez, N. F., Heegsma, J., Sydor, S. & Faber, K. N., Sep-2019, In : Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids. 1864, 9, p. 1258-1267 10 p.

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  • Hormone-sensitive lipase is a retinyl ester hydrolase in human and rat quiescent hepatic stellate cells

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DOI

Hepatic stellate cells (HSC) store vitamin A as retinyl esters and control circulating retinol levels. Upon liver injury, quiescent (q)HSC lose their vitamin A and transdifferentiate to myofibroblasts, e.g. activated (a)HSC, which promote fibrosis by producing excessive extracellular matrix. Adipose triglyceride lipase/patatin-like phospholipase domain-containing protein 2 (ATGL/PNPLA2) and adiponutrin (ADPN/PNPLA3) have so far been shown to mobilize retinol from retinyl esters in HSC. Here, we studied the putative role of hormone-sensitive lipase (HSL/LIPE) in HSC, as it is the major retinyl ester hydrolase (REH) in adipose tissue.

Lipe/HSL expression was analyzed in rat liver and primary human and rat qHSC and culture-activated aHSC. Retinyl hydrolysis was analyzed after Isoproterenol-mediated phosphorylation/activation of HSL.

Primary human HSC contain 2.5-fold higher LIPE mRNA levels compared to hepatocytes. Healthy rat liver contains significant mRNA and protein levels of HSL/Lipe, which predominates in qHSC and cells of the portal tree. Q-PCR comparison indicates that Lipe mRNA levels in qHSC are dominant over Pnpla2 and Pnpla3. HSL is mostly phosphorylated/activated in qHSC and partly colocalizes with vitamin A-containing lipid droplets. Lipe/HSL and Pnpla3 expression is rapidly lost during HSC culture-activation, while Pnpla2 expression is maintained. HSL super-activation by isoproterenol accelerates loss of lipid droplets and retinyl palmitate from HSC, which coincided with a small, but significant reduction in HSC proliferation and suppression of Collagen1A1 mRNA and protein levels.

In conclusion, HSL participates in vitamin A metabolism in qHSC. Equivalent activities of ATGL and ADPN provide the healthy liver with multiple routes to control circulating retinol levels.

Original languageEnglish
Pages (from-to)1258-1267
Number of pages10
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1864
Issue number9
Publication statusPublished - Sep-2019

    Keywords

  • Hormone-sensitive lipase (HSL), Hepatic stellate cell (HSC), Vitamin A, Retinyl ester hydrolase, Lipases, ADIPOSE TRIGLYCERIDE LIPASE, VITAMIN-A, BILE-ACID, EXPRESSION, MICE, ACYLTRANSFERASE, MOBILIZATION, CAROTENOIDS, ABSORPTION, TRANSPORT

ID: 90146822