Journal
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS
Volume 1862, Issue 2, Pages 176-187Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbalip.2016.10.013
Keywords
Hepatic stellate cells; LRAT; DGAT1; Retinyl esters; Lipid droplets; Lipidomics
Funding
- Seventh Framework Programme of the EU-funded LipidomicNet project [202272]
- Government of Malaysia [KPT(BS)811221145457]
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Hepatic stellate cells (HSCs) play an important role in liver physiology and under healthy conditions they have a quiescent and lipid-storing phenotype. Upon liver injury, HSCs are activated and rapidly lose their retinyl ester containing lipid droplets. To investigate the role of lecithin:retinol acyltransferase (LRAT) and acylCoA:diacylglycerol acyltransferase 1 (DGAT1) in retinyl ester synthesis and lipid droplet dynamics, we modified LC-MS/MS procedures by including multiple reaction monitoring allowing unambiguous identification and quantification of all major retinyl ester species. Quiescent primary HSCs contain predominantly retinyl palmitate. Exogenous fatty acids are a major determinant in the retinyl ester species synthesized by activated HSCs and LX-2 cells, indicating that HSCs shift their retinyl ester synthesizing capacity from LRAT to DGAT1 during activation. Quiescent LRAT(-/-) HSCs retain the capacity to synthesize retinyl esters and to store neutral lipids in lipid droplets ex vivo. The median lipid droplet size in LRAT(-/-) HSCs (1080 nm) is significantly smaller than in wild type HSCs (1618 nm). This is a consequence of an altered lipid droplet size distribution with 50.5 +/- 9.0% small (700 nm) lipid droplets in LRAT(-/-) HSCs and 25.6 +/- 1.4% large (1400-2100 nm) lipid droplets in wild type HSC cells. Upon prolonged (24 h) incubation, the amounts of small (<= 700 nm) lipid droplets strongly increased both in wild type and in LRAT(-/-) HSCs, indicating a dynamic behavior in both cell types. The absence of retinyl esters and reduced number of lipid droplets in LRAT-deficient HSCs in vivo will be discussed. (C) 2016 Elsevier B.V. All rights reserved.
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