Rapid turnover of apolipoprotein C-III-containing triglyceride-rich lipoproteins contributing to the formation of LDL subfractions.
The 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.
Zheng
Chunyu
C
Department of Nutrition, Harvard School of Public Health, Boston, MA 02115, USA.
Khoo
Christina
C
Ikewaki
Katsunori
K
Sacks
Frank M
FM
D053305:Apolipoprotein C-III / Q000378:metabolism*; D001057:Apolipoproteins E / Q000378:metabolism; D008078:Cholesterol, LDL / Q000378:metabolism*; D015243:Cholesterol, VLDL / Q000378:metabolism; D005260:Female; D006801:Humans; D015228:Hypertriglyceridemia / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism*
D053305:Apolipoprotein C-III; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D014280:Triglycerides