Objective-We have established a hereditary postprandial hypertriglyceridemic (PHT) rabbit. The present study was designed to define whether this rabbit model represents both insulin resistance and central obesity. Methods and Results-Body weight, abdominal circumference, visceral fat weight, and glucose tolerance were compared between PHT and Japanese white (JW) rabbit. Plasma levels of triglycerides (TG), total cholesterol (TC), glucose, and insulin were measured before and after feeding. Abdominal circumference of PHT rabbit was larger than that of JW rabbit, with no difference in body mass index. Visceral fat accumulation was noted as obvious in mesenterium, retroperitoneal space, and epididymal area. Plasma TG and TC levels were high preprandially and markedly increased postprandially in PHT rabbit compared with JW rabbit. Although plasma glucose levels were comparable in both groups, plasma insulin levels were elevated in PHT rabbit. Glucose tolerance tests indicated that plasma insulin levels in PHT rabbit were consistently higher than in JW rabbit. A positive correlation was observed between plasma insulin levels and visceral fat weight in PHT rabbit. underlying milieu of atherosclerosis. 1-3 Recent US statistics show that metabolic syndrome affects Ϸ1 in 4 adults and that the incidence of metabolic syndrome is sharply increasing with the growing population of obese individuals with visceral adiposity due partly to overeating, lack of physical exercise, and a high-fat diet. 4 In light of its clinical significance, development of therapeutic remedies for metabolic syndrome is of prime importance and therefore the establishment of an animal model is urgently required. Conclusions-PHTMetabolic syndrome is characterized by a clustering of several cardiovascular risk factors in a single individual, including dyslipidemia, centrally distributed adiposity, hypertension, and syndromes of glucose intolerance. Although multiple disorders were partly modeled by glucose intolerance in heritable rodent models, 5,6 lipid metabolism differs considerably between humans and rodents (eg, lack of cholesteryl ester transfer protein, differences in the apoB synthesis pathway). 7-9 To apply contemporary approaches using genetically engineered mice or translucent zebrafish, genetic phenotypes of metabolic syndrome remain too complex.An animal model of familiar hypercholesterolemia is unique in Watanabe heritable hyperlipidemic (WHHL) rabbit, because it closely resembles cholesterol metabolism in humans. We successfully segregated a hypertriglyceridemic type of WHHL (WHHL-TGH) rabbit, and then established a postprandial hypertriglyceridemic (PHT) rabbit from a cross between a normal Japanese white (JW) rabbit and a WHHL-TGH rabbit. 10 The present study was aimed to clarify the levels of central obesity and glucose intolerance in our newly established animal model of human disease. Materials and Methods AnimalsMale 8-to 16-month-old PHT rabbits (number of rabbits: 19) and 10-to 17-month-old JW rabbits (number of rabbits: 6; Shira...

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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...

Rabbits with hereditary postprandial hypertriglyceridemia exhibit central obesity and are regarded as a reliable model for metabolic syndrome. This study was performed to gain insight into the affected process of lipid metabolism and into the causative genes of the postprandial hypertriglyceridemia rabbits. Eleven genes that play key roles in lipid metabolism were selected, their mRNA levels were assessed by quantitative PCR, and their expressions were compared among postprandial hypertriglyceridemia rabbits using Japanese white rabbits as the control. Two genes appeared to be in causal connection with postprandial hypertriglyceridemia, and these were regarded as likely candidates for the pathogenesis. One was the fatty acid synthase gene, which had an expression constitutively higher in postprandial hypertriglyceridemia rabbits than in Japanese white rabbits during the fasting state and reached quite high levels after feeding. The other was the gene for hepatic triglyceride lipase with an expression that was approximately one order lower than that found in the Japanese white rabbits. The low plasma hepatic triglyceride lipase activities were consistent with the low levels of the transcript in the livers of the postprandial hypertriglyceridemia rabbits. Thus, elevated fatty acid synthesis and defected lipid hydrolysis together would cause the postprandial hypertriglyceridemia in postprandial hypertriglyceridemia rabbits.