ATGL and DGAT1 are involved in the turnover of newly synthesized triacylglycerols in hepatic stellate cells[S]

• Main Authors: Maidina Tuohetahuntila, Martijn R. Molenaar, Bart Spee, Jos F. Brouwers, Martin Houweling, Arie B. Vaandrager, J. Bernd Helms
• Format: Article
• Language: English
• Published: Elsevier 2016-07-01
• Series: Journal of Lipid Research
• Subjects: vitamin A; lipase; lipolysis and fatty acid metabolism; lipid droplets; lipidomics; heavy isotope labeling
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520351543

Hepatic stellate cell (HSC) activation is a critical step in the development of chronic liver disease. During activation, HSCs lose their lipid droplets (LDs) containing triacylglycerol (TAG), cholesteryl esters (CEs), and retinyl esters (REs). Here we aimed to investigate which enzymes are involved in LD turnover in HSCs during activation in vitro. Targeted deletion of the Atgl gene in mice HSCs had little effect on the decrease of the overall TAG, CE, and RE levels during activation. However, ATGL-deficient HSCs specifically accumulated TAG species enriched in PUFAs and degraded new TAG species more slowly. TAG synthesis and levels of PUFA-TAGs were lowered by the diacylglycerol acyltransferase (DGAT)1 inhibitor, T863. The lipase inhibitor, Atglistatin, increased the levels of TAG in both WT and ATGL-deficient mouse HSCs. Both Atglistatin and T863 inhibited the induction of activation marker, α-smooth muscle actin, in rat HSCs, but not in mouse HSCs. Compared with mouse HSCs, rat HSCs have a higher turnover of new TAGs, and Atglistatin and the DGAT1 inhibitor, T863, were more effective. Our data suggest that ATGL preferentially degrades newly synthesized TAGs, synthesized by DGAT1, and is less involved in the breakdown of preexisting TAGs and REs in HSCs. Furthermore a large change in TAG levels has modest effect on rat HSC activation.