Very low density lipoprotein triglyceride metabolism in relatives of hypertriglyceridemic probands. Evidence for genetic control of triglyceride removal.
The production and catabolism of very low density lipoprotein triglycerides (VLDL-TG) were determined in 11 index patients with primary hypertriglyceridemia and in their 70 first-degree relatives. In the probands the mean value for VLDL-TG production rate was twice normal, and the mean fractional catabolic rate (FCR) was reduced to 50% from normal. A similar kinetic pattern was also observed in most hypertriglyceridemic relatives. In the normotriglyceridemic relatives the mean values of both kinetic parameters were comparable to those of controls. No kinetic differences were observed between families with familial hypertriglyceridemia, familial combined hyperlipidemia, or genetically unclassified hypertriglyceridemia (all diagnosed by lipoprotein phenotypes). Thus, no explanation for the phenotypic differences between the two forms of familial hyperlipoproteinemia was found in plasma VLDL-TG metabolism. When the families were grouped according to the VLDL-TG production rate of the proband, there was no significant difference between the VLDL-TG production rates of relatives of "overproducer" probands and relatives of the probands with normal VLDL-TG production rate. In contrast, relatives of low FCR probands had significantly lower mean FCR than the relatives of probands with a normal FCR. This difference in FCR was present both in hypertriglyceridemic and normotriglyceridemic relatives. These results suggest that the catabolism (lipolysis) of VLDL-TG is under genetic control, whereas the VLDL-TG production rate is mainly related to obesity. It is likely that hypertriglyceridemia often develops on the basis of VLDL overproduction in individuals who have a genetically low VLDL triglyceride removal (lipolytic) capacity.
Sane
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Third Department of Medicine, University of Helsinki Central Hospital, Finland.
Nikkilä
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EA
D000293:Adolescent; D000328:Adult; D001835:Body Weight; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000235:genetics; D006953:Hyperlipoproteinemia Type IV / Q000097:blood* / Q000235:genetics; D007700:Kinetics; D008066:Lipolysis; D008079:Lipoproteins, VLDL / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D014280:Triglycerides / Q000097:blood* / Q000235:genetics
D008079:Lipoproteins, VLDL; D014280:Triglycerides