Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions

Zheng, CarsonKhoo, C.Ikewaki, K.Sacks, Frank2017-02-072007Zheng, C., C. Khoo, K. Ikewaki, and F. M. Sacks. 2007. “Rapid Turnover of Apolipoprotein C-III-Containing Triglyceride-Rich Lipoproteins Contributing to the Formation of LDL Subfractions.” The Journal of Lipid Research 48 (5) (February 10): 1190–1203. doi:10.1194/jlr.p600011-jlr200.0022-2275http://nrs.harvard.edu/urn-3:HUL.InstRepos:30205710The atherogenicity theory for triglyceride-rich lipoproteins (TRLs; VLDL + intermediate density lipoprotein) generally cites the action of apolipoprotein C-III (apoC-III), a component of some TRLs, to retard their metabolism in plasma. We studied the kinetics of multiple TRL and LDL subfractions according to the content of apoC-III and apoE in 11 hypertriglyceridemic and normolipidemic persons. The liver secretes mainly two types of apoB lipoproteins: TRL with apoC-III and LDL without apoC-III. Approximately 45% of TRLs with apoC-III are secreted together with apoE. Contrary to expectation, TRLs with apoC-III but not apoE have fast catabolism, losing some or all of their apoC-III and becoming LDL. In contrast, apoE directs TRL flux toward rapid clearance, limiting LDL formation. Direct clearance of TRL with apoC-III is suppressed among particles also containing apoE. TRLs without apoC-III or apoE are a minor, slow-metabolizing precursor of LDL with little direct removal. Increased VLDL apoC-III levels are correlated with increased VLDL production rather than with slow particle turnover. Finally, hypertriglyceridemic subjects have significantly greater production of apoC-III-containing VLDL and global prolongation in residence time of all particle types. ApoE may be the key determinant of the metabolic fate of atherogenic apoC-III-containing TRLs in plasma, channeling them toward removal from the circulation and reducing the formation of LDLs, both those with apoC-III and the main type without apoC-III.en-USkineticsstable isotopesapolipoprotein B-100apolipoprotein Elow density lipoproteinRapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractionsJournal Article2017-02-0710.1194/jlr.P600011-JLR200