Further Observations on the Activation and Inhibition of Lipoprotein Lipase by Apolipoproteins

Abstract

ApoC-II was the only apolipoprotein from human very low density lipoprotein that activated rat adipose tissue lipoprotein lipase. Activation was blocked by antiserum against apoC-II. Addition of increasing amounts of activator did not alter the apparent K m of lipoprotein lipase (0.32 mM triolein), but it did produce a progressive increase in the apparent V max from 0.8 to 2.2 µmoles free fatty acid/mg hour -1 . Substrate concentrations above 1.27 mM triolein diminished activation by 0.25-5.0 µg/ml of apoC-II as much as 20%. Reversal of this apparent substrate inhibition was achieved by increasing the activator concentration to 50.0 µg/ml. Each of five nonactivating apolipoproteins-apoC-I, C-III-1, C-III-2, A-I, and A-II-inhibited lipoprotein lipase up to 85-100%. ApoC-II also produced less inhibition under appropriate conditions. Inhibition was dependent on apoprotein concentration, inversely related to substrate triglyceride concentration, and unobserved with nonlipoprotein proteins. The inhibitory capacity of the nonactivating apolipoproteins was about the same, was independent of apoC-II concentration, and occurred when the ratio of nonactivator apoprotein to triglyceride exceeded 3% (w/w). It is possible that these apoproteins function partly to modulate the hydrolysis of very low density lipoprotein triglyceride by lipoprotein lipase.

Apolipoprotein CIII promotes Ca 2+ -dependent β cell death in type 1 diabetes

“…The concentration of apoCIII has been reported to be between 60-140 g͞ml in control subjects and 90-270 g͞ml in diabetics (9,19,20,(24)(25)(26)(27). These variations may to a certain extent reflect the fact that various methods have been used for the determinations.…”

Genotype/phenotype relationships in HNF-4alpha/MODY1: haploinsufficiency is associated with reduced apolipoprotein (AII), apolipoprotein (CIII), lipoprotein(a), and triglyceride levels.

“…These transcriptional changes in the liver lead to a decrease in the serum levels of these factors. Lowered triglyceride concentrations may result from increased lipoprotein lipase (LPL) activity because apo(CIII) is an inhibitor of LPL activity in vitro (32), and transgenic mice overexpressing human apo(CIII) have elevated triglyceride levels in plasma because of the presence of enlarged triglyceride-rich lipoproteins with increased apo(CIII) levels (33). Low apo(AII) levels may also contribute to decreased triglyceride levels because overexpression of apo(AII) in transgenic mice leads to hypertriglyceridemia (34), and apo(AII) deficiency in knockout mice is associated with low free fatty acid levels (35).…”

Apolipoprotein C-III(Lys58----Glu). Identification of an apolipoprotein C-III variant in a family with hyperalphalipoproteinemia.

“…The physiological function ofapo C-III is not yet fully understood. In vitro, high concentrations of apo C-III have been shown to inhibit lipoprotein lipase (LPL) (16,17) and hepatic triglyceride lipase (18), enzymes responsible for the clearance of triglyceride rich particles from the plasma. In contrast to normal plasma, apo A-I/apo C-III deficient plasma is not able to inhibit LPL activity, thus supporting the hypothesis that apo C-III also inhibits LPL in vivo (19).…”