Overproduction of a kinetic subclass of VLDL-apoB, and direct catabolism of VLDL-apoB in human endogenous hypertriglyceridemia: an analytical model solution of tracer data.
To investigate the participation of the major apoprotein involved in triglyceride transport in the pathogenesis of endogenous hypertriglyceridemia, five kinetic studies of apoprotein B were conducted in volunteer normolipidemic subjects and six studies in four patients with endogenous hypertriglyceridemia. The transport of apoprotein B within four kinetic subclasses of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was studied by injection of [75Se]selenomethionine. A 24-fold increase in the entry of newly synthesized apoprotein B at the initial kinetic subclass of the four-compartment VLDL delipidation sequence characterized the hypertriglyceridemic studies relative to normal subjects. Moreover, approximately 75 mg/kg per day of VLDL-B turnover reflected direct catabolism independent of conversion to IDL and/or to LDL, in contrast to the 8 mg/kg per day observed in controls. IDL-B was derived from VLDL-B in both normal and hypertriglyceridemic subjects, and was responsible for greater than 70% of all LDL-B synthesis. LDL-B pool size and turnover were indistinguishable in hypertriglyceridemic subjects from that observed in normal subjects. These studies suggest that two kinetic phenomena may characterize the pathophysiology of endogenous hypertriglyceridemia: a) over-production of apoB within a kinetic subclass of VLDL and b) preferential catabolism of hypertriglyceridemic VLDL without prior conversion to IDL/LDL.
D000328:Adult; D001053:Apolipoproteins / Q000378:metabolism*; D001055:Apolipoproteins B; D005260:Female; D006801:Humans; D006951:Hyperlipoproteinemias / Q000378:metabolism*; D007700:Kinetics; D008074:Lipoproteins / Q000097:blood; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D011868:Radioisotopes; D012016:Reference Values; D012643:Selenium / Q000097:blood
D001053:Apolipoproteins; D001055:Apolipoproteins B; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D011868:Radioisotopes; D012643:Selenium