Adipose triglyceride lipase is involved in the mobilization of triglyceride and retinoid stores of hepatic stellate cells.
Hepatic stellate cells (HSCs) store triglycerides (TGs) and retinyl ester (RE) in cytosolic lipid droplets. RE stores are degraded following retinoid starvation or in response to pathogenic stimuli resulting in HSC activation. At present, the major enzymes catalyzing lipid degradation in HSCs are unknown. In this study, we investigated whether adipose triglyceride lipase (ATGL) is involved in RE catabolism of HSCs. Additionally, we compared the effects of ATGL deficiency and hormone-sensitive lipase (HSL) deficiency, a known RE hydrolase (REH), on RE stores in liver and adipose tissue. We show that ATGL degrades RE even in the presence of TGs, implicating that these substrates compete for ATGL binding. REH activity was stimulated and inhibited by comparative gene identification-58 and G0/G1 switch gene-2, respectively, the physiological regulators of ATGL activity. In cultured primary murine HSCs, pharmacological inhibition of ATGL, but not HSL, increased RE accumulation. In mice globally lacking ATGL or HSL, RE contents in white adipose tissue were decreased or increased, respectively, while plasma retinol and liver RE levels remained unchanged. In conclusion, our study shows that ATGL acts as REH in HSCs promoting the degradation of RE stores in addition to its established function as TG lipase. HSL is the predominant REH in adipocytes but does not affect lipid mobilization in HSCs.
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Ulrike
U
Taschler
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Renate
R
Schreiber
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Chandramohan
C
Chitraju
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Gernot F
GF
Grabner
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Matthias
M
Romauch
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Heimo
H
Wolinski
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Guenter
G
Haemmerle
Institute of Organic Chemistry, Graz University of Technology, Graz 8010, Austria.
Rolf
R
Breinbauer
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria.
Rudolf
R
Zechner
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria. Electronic address: achim.lass@uni-graz.at.
Achim
A
Lass
Institute of Molecular Biosciences, University of Graz, Graz 8010, Austria. Electronic address: robert.zimmermann@uni-graz.at.
Robert
R
Zimmermann
D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D019556:COS Cells; D002265:Carboxylic Ester Hydrolases / Q000235:genetics / Q000378:metabolism; D002522:Chlorocebus aethiops; D005260:Female; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D008049:Lipase / Q000502:physiology*; D050356:Lipid Metabolism / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D012176:Retinoids / Q000378:metabolism*; D002787:Sterol Esterase / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*; D000217:Acyltransferases
D002265:Carboxylic Ester Hydrolases; D008049:Lipase; D012176:Retinoids; D002787:Sterol Esterase; D014280:Triglycerides; C022523:retinyl esterase; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases
Adipose triglyceride lipase; Hepatic stellate cells; Retinoids; Retinyl ester