Clearance defects in primary chylomicronemia: A study of tissue lipoprotein lipase activities

Abstract

Tissue and postheparin lipoprotein lipase (LPL) activities were assayed in a heterogeneous group of eight chylomicronemic subjects ranging in age from 15 years to 55 years. Three patients, presenting with the classical genetic and clinical features of type I hyperlipoproteinemia, had virtually absent adipose tissue LPL activity and markedly reduced muscle LPL activity (between 5% and 20% of normal). A fourth patient, with a similar but more benign lipoprotein and clinical phenotype, showed reduced adipose tissue LPL activity (10% of control) but retained essentially normal muscle enzyme. This patient represents a variant form of familial LPL deficiency. Two of the four remaining patients presented with typical features of adult type V hyperlipoproteinemia associated with familial hypertriglyceridemia (type IV and V phenotypes) in first-degree relatives. Adipose tissue LPL activities were 25% to 35% of the control mean in these patients, but muscle activities were normal or elevated. A third patient had suggestively similar tissue enzyme levels, but a family study could not be carried out. The eighth patient presented with a brittle type V phenotype, normolipidemia in the two first-degree relatives available for study and normal lipolytic activity in adipose tissue, muscle, and postheparin plasma assayed against a 14C-triolein substrate. An oral fat load in this patient, however, led to a marked but transient increase in ligh scattering suggesting defective clearance. Mixing experiments in vitro using a chylomicron substrate strongly suggested an extrinsic defect of lipolysis due to the inhibitory effect of excess very low density lipoprotein peptides, presumably apo C-III. The data were also compatible with the proposal that normal in vivo lipolysis may be regulated by the balance between activatory and inhibitory peptides. This study, therefore, has revealed the existence of four distinct lipolytic defects in a group of chylomicronemic subjects. Phenotypic expression probably reflects a balance between oversecretion and reduced clearance as well as the nature and severity of the underlying defect or defects.