This article is available online at http://www.jlr.org TG levels ( 10 ); however, a difference in fasting TG level only partially accounts for the interindividual variation in the magnitude of postprandial lipemia. Indeed, it is known that the postprandial TG response is infl uenced by genetic background, dietary composition, physical activity, age, gender, and obesity ( 11-13 ).To examine the factors that affect postprandial hypertriglyceridemia and their mechanisms and effects on arteries in vivo, a mouse model of hypertriglyceridemia in response to dietary fat is required ( 14 ). However, no rodent models of postprandial hypertriglyceridemia have been reported. This is possibly due to the lack of cholesteryl ester transfer protein (CETP) in rodents, a hypothesis supported by the fi nding that CETP transgenic mice have increased postprandial hypertriglyceridemia ( 15 ) and that CETP defi ciency in humans results in signifi cantly reduced fasting and postprandial hypertriglyceridemia with an increase in HDL cholesterol ( 16 ). In humans, postprandial lipemia has been evaluated after induction by an oral fatload or a high-fat (HF) diet ( 17 ). During our studies of dietary effects on fatty liver and obesity, we found that the blood TG concentration in response to changes in dietary fat differed markedly between ddY and C57BL/6J mice. When a single HF diet was given to 24 h-fasted ddY and C57BL/6J mice, ddY mice showed a 3-fold increase in blood TG concentration after 3 h feeding either a saffl ower oil-rich or a butter-rich diet ( 18, 19 ), whereas there was no signifi cant increase in TG concentration in C57BL/6J mice ( 20 ).In this study, we compared TG responses after oral ingestion of fat in several strains of mice. ddY mice displayed marked postprandial hypertriglyceridemia in response to dietary fat, representing a suitable animal model of postprandial hyperlipidemia.Abstract Postprandial hyperlipidemia (lipemia) is a risk factor for atherosclerosis. However, mouse models of postprandial hyperlipidemia have not been reported. Here, we report that ddY mice display marked postprandial hypertriglyceridemia in response to dietary fat. In ddY mice, the fasting serum total triacylglyceride (TG) concentration was 134 mg/dl, which increased to 571 mg/dl after an intragastric saffl ower oil load (0.4 ml/mouse). In C57BL/6J mice, these concentrations were 57 and 106 mg/dl, respectively. By lipoprotein analysis, ddY mice showed increases in chylomicron-and VLDL-sized TG fractions (remnants and VLDL) after fat load. In C57BL/6J mice, post-heparin plasma LPL activity after fat load was increased 4.8-fold relative to fasting. However, in ddY mice, the increase of LPL activity after fat load was very small (1.2-fold) and not signifi cant. High fat feeding for 10 weeks led to obesity in ddY mice. A difference in LPL amino acid composition between C57BL/6J and ddY mice was detected but was deemed unlikely to cause hypertriglyceridemia because hypertriglyceridemia was not evident in other strains harboring the ddY-type LPL ...
