Altered lipid droplet dynamics in hepatocytes lacking triacylglycerol hydrolase expression.
Lipid droplets (LDs) form from the endoplasmic reticulum (ER) and grow in size by obtaining triacylglycerols (TG). Triacylglycerol hydrolase (TGH), a lipase residing in the ER, is involved in the mobilization of TG stored in LDs for the secretion of very-low-density lipoproteins. In this study, we investigated TGH-mediated changes in cytosolic LD dynamics. We have found that TGH deficiency resulted in decreased size and increased number of LDs in hepatocytes. Using fluorescent fatty acid analogues to trace LD formation, we observed that TGH deficiency did not affect the formation of nascent LDs on the ER. However, the rate of lipid transfer into preformed LDs was significantly slower in the absence of TGH. Absence of TGH expression resulted in increased levels of membrane diacylglycerol and augmented phospholipid synthesis, which may be responsible for the delayed lipid transfer. Therefore, altered maturation (growth) rather than nascent formation (de novo synthesis) may be responsible for the observed morphological changes of LDs in TGH-deficient hepatocytes.
Wang
Huajin
H
Department of Cell Biology, University of Alberta, Edmonton, Alberta T6G 2S2, Canada.
Wei
Enhui
E
Quiroga
Ariel D
AD
Sun
Xuejin
X
Touret
Nicolas
N
Lehner
Richard
R
D000818:Animals; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000201:enzymology; D005260:Female; D017353:Gene Deletion; D022781:Hepatocytes / Q000187:drug effects / Q000201:enzymology*; D008049:Lipase / Q000172:deficiency* / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D019301:Oleic Acid / Q000494:pharmacology; D010743:Phospholipids / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D014280:Triglycerides / Q000378:metabolism
D004075:Diglycerides; D010743:Phospholipids; D014280:Triglycerides; D019301:Oleic Acid; D008049:Lipase
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