Apolipoprotein B metabolism in subjects with deficiency of apolipoproteins CIII and AI. Evidence that apolipoprotein CIII inhibits catabolism of triglyceride-rich lipoproteins by lipoprotein lipase in vivo.

Abstract

Previous data suggest that apolipoprotein (apo) CIII may inhibit both triglyceride hydrolysis by lipoprotein lipase (LPL) and apo E-mediated uptake of triglyceride-rich lipoproteins by the liver. We studied apo B metabolism in very low density (VLDL), intermediate density (IDL), and low density lipoproteins (LDL) in two sisters with apo CiII-apo AI deficiency. The subjects had reduced levels of VLDL triglyceride, normal LDL cholesterol, and near absence of high density lipoprotein (HDL) cholesterol. Compartmental analysis of the kinetics of apo B metabolism after injection of '"I-VLDL and 131I-LDL revealed fractional catabolic rates (FCR) for VLDL apo B that were six to seven times faster than normal. Simultaneous injection of V3Hjglycerol demonstrated rapid catabolism of VLDL triglyceride. VLDL apo B was rapidly and efficiently converted to IDL and LDL. The FCR for LDL apo B was normal.In vitro experiments indicated that, although sera from the apo CII-apo-AI deficient patients were able to normally activate purified LPL, increasing volumes of these sera did not result in the progressive inhibition of LPL activity demonstrable with normal sera. Addition of purified apo CIII to the deficient sera resulted in 20-50% reductions in maximal LPL activity compared with levels of activity attained with the same volumes of the native, deficient sera. These in vitro studies, together with the in vivo results, indicate that in normal subjects apo CIII can inhibit the catabolism of triglyceride-rich lipoproteins by lipoprotein lipase.

Apolipoprotein CIII polymorphism and triglyceride levels of a Japanese population living in Southern Brazil

“…The genetically determined deficiency of apo-CIII has been shown to increase the rate of TG clearance from plasma by 6-to 7-fold (31). Over-expression of apo-CIII produces hypertriglyceridemia in transgenic mouse models via inhibition of clearance of TG-rich particles (32).…”

No Apparent Impact of Meal Glycemic Index on Postprandial Lipid Response in Lean and Abdominally Obese Women

“…Apo C-3, a protein produced by the liver, inhibits lipoprotein lipase. Elevated levels of apo C-3 are associated with higher levels of triglyceride through reduced clearance of triglyceride-rich lipoproteins [46,47]. Apo C-3 was slightly higher, but not significantly, in the insulin resistant subjects.…”

Impact of bariatric surgery on apolipoprotein C-III levels and lipoprotein distribution in obese human subjects

“…Second, it is well known that apoC-III is an inhibitor of LPL activity. 19 Third, several studies have shown that apoC-III inhibits receptor-mediated uptake of TRL by the liver. 21,22 Kinetic studies using tracer methodology have confirmed that VLDL-apoC-III is overproduced in overweight insulin-resistant subjects, 15 in hypertriglyceridemic subjects compared with controls, 53 and in centrally, obese men compared with controls.…”

“…13 Plasma apoC-III concentration is strongly correlated with plasma triglyceride (TG) concentration 14,15 and is increased in insulin-resistant states (overweight or obesity 15 and type II diabetes 16,17 ). Elevated apoC-III has been postulated to contribute to the atherogenic dyslipidemia by the impairment of TRL and HDL metabolism including increased VLDL production and secretion, 18 disturbance of TRL clearance by inhibiting LPL 19 or hepatic lipase, 20 and interfering with TRL and their remnant binding to hepatic lipoprotein receptors. 21,22 Beyond the effects of apoC-III on TRL and HDL metabolism, this apolipoprotein has also been shown to promote inflammation and endothelial cell dysfunction, potentially contributing to atherosclerosis and cardiovascular disease.…”