Kinetic analysis of apolipoproteins in postprandial hypertriglyceridaemia rabbits

Abstract

The postprandial hypertriglyceridaemia (PHT) rabbit, developed as a new animal model of metabolic syndrome, is characterized by PHT, central obesity and glucose intolerance. For detailed investigation of lipid metabolism characteristics in PHT rabbit, the plasma levels of apolipoproteins A-I, B, C-II, C-III and E were measured. Movements of apolipoproteins B100 and B48 were investigated using sodium dodecyl sulphate-polyacrylamide gel electrophoresis to determine whether postprandially increased triglyceride is exogenous or endogenous. The level of apolipoproteins A-I, B, C-II and E were increased in PHT rabbit after feeding. Apolipoproteins B100 and B48 were detected in the plasma fraction of d , 1.006 g/mL of the PHT rabbit. The postprandial increase in apolipoprotein B in the PHT rabbit reflects a numerical increase in lipoprotein particles in the blood; the increase in apolipoproteins C-II and E suggests some disturbance in lipoprotein catabolism. Apolipoprotein B48 was detected postprandially in PHT rabbits. These results suggest that delayed catabolism of exogenous lipids caused the retention of chylomicron remnants in the blood. Results also suggest that activities of the lipolytic enzyme lipoprotein lipase and hepatic triglyceride lipase were deficient and that the hepatic uptake of exogenous lipoproteins was delayed in the PHT rabbit. Especially, for examining remnant hyperlipoproteinaemia in humans, PHT rabbit is an excellent animal model for hypertriglyceridaemia research. Ischaemic heart disease is closely related to the plasma cholesterol (CHO) level. However, results of recent studies have demonstrated that not all patients developing ischaemic heart disease have hypercholesterolaemia 1 and that elevated levels of serum triglycerides (TG) increase the risk of ischaemic heart disease.2,3 Furthermore, metabolic syndrome, a condition in which central obesity is complicated by multiple risk factors of atherosclerosis (hypertriglyceridaemia, glucose intolerance and hypertension), has recently been suggested to increase the risk of ischaemic heart disease. From the Watanabe heritable hyperlipidaemic (WHHL) rabbit, Tomoike et al. of the Yamagata University Faculty of Medicine selectively bred the WHHL-TGH (triglyceride-high) rabbit, in which serum CHO and TG levels were both high, and the WHHL-TGL (triglyceridelow) rabbit, in which the CHO level was high but the TG level was normal.4 Tomoike et al. also developed the postprandial hypertriglyceridaemic (PHT) rabbit model, which showed normal serum TG and CHO levels during fasting, but an abnormally high level of TG alone postprandially. 4 The PHT rabbit, which showed a high postprandial TG level, was derived from the mutant F2 hybrid by crossbreeding between the Japanese White (JW) rabbit and the WHHL-TGH rabbit.The PHT rabbit was derived from the WHHL-TGH rabbit by eliminating the factor of hypercholesterolaemia and selecting individuals who showed PHT. Actually, the PHT rabbit strain is considered to be polygenic.5 Expected to be a novel animal m...

The Role of Hypertriglyceridemia in the Development of Atherosclerosis and Endothelial Dysfunction

“…Previously it was reported that the retention of chylomicron remnants was caused by the delayed catabolism of exogenous lipids in the blood of PHT. In addition, the lipolytic enzyme lipoprotein lipase and hepatic triglyceride lipase were deficient and that the hepatic uptake of exogenous lipoproteins was delayed in the PHT rabbit [17]. In contrast, cholesterol levels in PHT rabbits were little changed even after feeding.…”

“…In fact, a previous report examined the kinetics of various apolipoproteins in PHT rabbit to elucidate the lipid metabolism in PHT. It was shown that apoprotein E, which is necessary for the uptake of chylomicron remnants by the liver, was increased postprandially in PHT [17]. In the SDS-PAGE experiments, apolipoprotein B100 was detected in the PHT rabbits before feeding, and apolipoproteins B100 and B48 were both detected 15 h after feeding.…”

“…In the SDS-PAGE experiments, apolipoprotein B100 was detected in the PHT rabbits before feeding, and apolipoproteins B100 and B48 were both detected 15 h after feeding. In contrast, in the JW rabbits, neither apolipoprotein B100 nor apolipoprotein B48 was detected before or after feeding [17]. Because apolipoprotein B48 was detected only in PHT after feeding, they suggested that exogenous lipoproteins remained unmetabolized after feeding in PHT [17].…”

Upregulation of fatty acid synthesis and the suppression of hepatic triglyceride lipase as a direct cause of hereditary postprandial hypertriglyceridemia in rabbits

“…LDLR mRNA in the liver was higher in PHT than in JW rabbits in the postprandial state, hence, the LDL uptake by the liver was not defected. Despite lower cholesterol contents in VLDL compared to LDL, the PHT rabbits contained extraordinarily high levels of VLDL, (9) suggesting that the VLDL-derived cholesterol would partly contribute to the high T-CHO values. Thus, the increase in the T-CHO can be explained by defected apolipoprotein clearance without increase in the CHO biosynthesis.…”

“…(8) Elevated secretion of VLDL from liver and temporary delaying of triglyceride degradation appears to be a direct cause of the postprandial hypertriglyceridemia. (9) …”