Oleate acutely stimulates the secretion of triacylglycerol by cultured rat hepatocytes by accelerating the emptying of the secretory compartment.
The acute effects of addition of oleate on the rate of triacylglycerol (TAG) secretion by cultured rat hepatocytes were studied by monitoring the use of endogenous (14C-prelabeled) acyl moieties and exogenous (3H-labeled) oleate for the synthesis of secreted TAG simultaneously. Inclusion of exogenous oleate in the medium stimulated the secretion of the endogenous 14C-labeled acyl moieties by 55-100%. To find out whether the stimulation was due to increased endogenous TAG mobilization or an increased rate of processing of TAG within the endoplasmic reticulum (ER) secretory machinery, use was made of the inhibition of apolipoprotein B (apoB) synthesis (but not degradation) by Ca2+ mobilization from the ER. Inhibition of apoB synthesis stopped entry of acyl moieties (from endogenous and exogenous sources) into the secretory pathway. However, even when entry of acyl moieties into the secretory pathway was totally inhibited, exogenous oleate was still able to stimulate (twofold) the secretion [14C]TAG, indicating that oleate stimulates the emptying of prelabeled TAG from the secretory compartment at a point distal to apoB synthesis and nascent particle formation. These data indicate that exogenous oleate, besides providing additional acyl moieties for incorporation into secreted TAG, stimulates the secretion of endogenous TAG in a manner (i) that is independent of effects on apoB synthesis and/or degradation and (ii) that involves the enhanced processing of TAG resident within the ER secretory pathway.
Zammit
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VA
Cellular Biochemistry, Hannah Research Institute, Ayr, Scotland, United Kingdom. zammitv@hri.sari.ac.uk
Lankester
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DL
D000818:Animals; D001055:Apolipoproteins B / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D002118:Calcium / Q000378:metabolism; D002451:Cell Compartmentation; D002478:Cells, Cultured; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism*; D019301:Oleic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019284:Thapsigargin / Q000494:pharmacology; D014280:Triglycerides / Q000378:metabolism*
D001055:Apolipoproteins B; D004791:Enzyme Inhibitors; D014280:Triglycerides; D019301:Oleic Acid; D019284:Thapsigargin; D002118:Calcium