The role of high density lipoprotein apolipoprotein CII in triglyceride metabolism
Authors: Kashyap M. L. , Srivastava L. S. , Hynd B. A. , Perisutti G. , Brady D. W. , Gartside P. , Glueck C. J. 
Published: November 2006

AbstractThe purpose of these studies was (a) to examine the relationship between total plasma triglycerides (TG) and the amount of apolipoprotein CII (apo CII) in triglyceride rich lipoproteins (TRL), and (b) to determine whether TRL could be enriched with apo CII in vitro. In 13 patients with primary endogenous hypertriglyceridemia, (log10) total plasma TG correlated inversely with the amount of apo CII per unit very low density lipoprotein (VLDL) protein (r=−0.76;p<0.005) and VLDL TG (r=−0.75; p<0.005). The potency of VLDL to activate milk lipoprotein lipase (LPL) in hydrolyzing triolein was studied in vitro. LPL activator potency per unit VLDL protein or VLDL TG correlated inversely with (log10) total plasma TG (r=−0.86 and r=−0.76, respectively; p<0.005). LPL activator potency per nM VLDL apo CII also correlated inversely with (log10) total plasma TG (r=−0.49; p<0.01). In seven patients with familial type V hyperlipoproteinemia, the average amount of apo CII in TRL protein was subnormal (5.86±0.62% vs 10.0±0.51% in normal subjects). The higher the (log10) total plasma TG, the lower was the apo CII content in TRL protein (r=−0.93; p<0.01). To determine the factors governing the distribution of apo CII between lipoproteins and whether TRL could be enriched with apo CII, five approaches were undertaken: (a)125I apo CII was added to mixtures of VLDL and HDL. The amount of labelled apo CII in VLDL was proportional to the ratio of VLDL to HDL. (b) TRL from four patients with familial type V hyperlipoproteinemia was incubated with high density lipoprotein (HDL) from a normal subject. An increase in the TRL/HDL ratio was associated with transfer of apo CII from HDL to TRL and a reciprocal transfer of non‐apo CII protein from TRL to HDL. Net apo CII enrichment of TRL protein was possible below a HDL/TRL protein ratio of ca. 6 under the experimental conditions. (c) A fixed amount of normal plasma feed of TRL was incubated with different amounts of TRL from two patients with familial type V hyperlipoproteinemia. The amount of apo CII that transferred from normal TRL free plasma to the patient's TRL was proportional to the amount of TRL in the mixture. (d) A doubling and tripling in the amount of apo CII in TRL was found when apo CII was added directly to TRL from a normal subject and TRL from a patient with familial type V hyperlipoproteinemia, respectively. (e) When apo CII was added directly to normal plasma and plasma from a patient with primary type IV hyperlipoproteinemia, the peptide was taken up mainly by VLDL and HDL, indicating enrichment of these fractions. The distribution of the added apo CII in each lipoprotein fraction resembled the distribution in the native plasma. TRL was isolated after addition of apo CII to plasma from two patients with familial types IV and V, respectively. Enrichment of TRL with apo CII was associated with an approximate 1.5‐fold increase in the LPL activator potency per unit TRL protein. These studies suggest that firstly, the amount of apo CII in TRL is inversely related to the severity of hypertriglyceridemia. Secondly, the distribution of apo CII between TRL and HDL is governed by the mass ratios of these two lipoprotein classes. Thirdly, plasma TRL and HDL have a reserve binding capacity of apo CII and fourthly, it is possible to enrich these lipoproteins with this functionally important peptide. Whether net enrichment of TRL with apo CII and also an increase in its biological activity to activate LPL in vitro is related to increased in vivo catabolic rate requires to be determined.