AB S T R A C T An abnormal triglyceride-rich lipoprotein has been isolated from some patients with chronic renal failure or severe hypertriglyceridemia. The abnormal lipoprotein was characterized by an increased content of apolipoprotein (apo) C-III-2 (57.5% of total apo C-III peptides compared with 35.5% for controls, P < 0.001) as characterized by isoelectric focusing and scanning densitometry. As determined by a substrate competition assay, the abnormal lipoprotein was a less efficient substrate for purified bovine milk lipoprotein lipase than control lipoproteins. Neuraminidase digestion of abnormal or control lipoprotein resulted in a reduction of the apo C-III-2 band with a corresponding increase in the region of apo C-III-0, which suggests that the increased content of apo C-III-2 in the abnormal is due to excessive sialylation of the C-III peptide. Limited incubation of the abnormal lipoproteins with neuraminidase caused a partial loss of sialic acid and resulted in a triglyceride-rich lipoprotein with a normal C-III-2:C-III-1 ratio. This preparation displayed normal substrate interaction with lipoprotein lipase. Three severely hypertriglyceridemic patients with the abnormal lipoprotein showed a marked reduction in serum triglyceride concentration, which is associated with a reversion to a normal C-peptide profile after dietary therapy. The results suggest that the extent of sialylation of the apo C-III peptide carried on triglyceride-rich lipoproteins may be critical for their interaction with lipoprotein lipase.
Summary. The activity of lipoprotein lipase (E.C.3.1.1.3.) has been measured in adipose tissue from insulin-independent diabetics with hypertriglyceridaemia, non-diabetics with hypertriglyceridaemia and control patients, all of whom were obese.Although all groups showed an increase of plasma insulin after oral glucose, both the diabetic and nondiabetic hypertriglyceridaemics had impaired activities of lipoprotein lipase in adipose tissue compared to the obese normals (p<0.02, p<0.03, respectively). A course of insulin therapy (20 u.o.d.) for one week increased the activity of lipoprotein lipase extracted from adipose tissue, lowered plasma triglycerides and improved triglyceride clearance from plasma in a group of diabetics with hypertriglyceridaemia (mean plasma triglyceride 8.7 mmol/1). Our results suggest that a feature in the development of insulin resistance in adult diabetics may be a failure of maintenance of key intracellular enzyme activities involved in lipid metabolism.
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