Low rates of apoB secretion from HepG2 cells result from reduced delivery of newly synthesized triglyceride to a “secretion-coupled” pool.

The present study was aimed at defining the roles of intracellular triglyceride pools in apolipoprotein B secretion from HepG2 cells. Oleic acid (0.2 mmol/L) in the medium stimulated both triglyceride synthesis and apolipoprotein B secretion. Stimulation of apolipoprotein B secretion was lost about 30-40 min after oleic acid was removed from the medium, despite the finding that most newly synthesized triglyceride was still present in the cells. This suggested that only a small fraction of newly synthesized triglyceride was transferred to a pool available for assembly of nascent apoB into lipoproteins. Using cell fractionation, we analyzed two triglyceride pools in HepG2 cells: a microsomal pool and a cytoplasmic pool. Oleic acid-induced increases in the microsomal pool were small and short-lived due to secretion; this pool, therefore, is a “secretion-coupled” pool. The large majority of newly synthesized triglyceride was in a cytosolic pool that was not associated with secretion of apoB. Dibutyryl cAMP treatment was associated with a 3-fold increase in the mobilization of the triglyceride droplets. Apolipoprotein B secretion, however, was not increased, suggesting that the amount of triglyceride that entered the “secretion-coupled” pool after hydrolysis and re-esterification of cytoplasmic triglyceride was inadequate to stimulate apolipoprotein B secretion. In summary, the majority of newly synthesized triglyceride, whether derived from exogenous or endogenous fatty acids, is rapidly shifted to a cytoplasmic pool that does not play a regulatory role in apolipoprotein B secretion. The presence of a very small “secretion-coupled” pool of triglyceride in HepG2 cells likely explains the high rates of degradation of nascent apolipoprotein B, and the low rates of secretion of lipid-poor lipoproteins.

Abstract licence: CC BY-NC-ND

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