Abstract
BackgroundExogenously hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. The responsible gene Smek2 was identified via linkage analysis using the original strain Sprague–Dawley (SD) rats. In this study, we compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats.MethodsMale 4-weeks-old ExHC and SD rats were fed a 1% cholesterol diet for 1 week. Serum and liver parameters were analyzed. Gene expression and enzyme activities related to TAG metabolism were also assessed.ResultsWe reproducibly observed higher serum cholesterol and lower hepatic TAG levels in ExHC rats than in SD rats. Golgi apparatus in the livers of ExHC rats secreted β-very-low-density lipoprotein (β-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the β-VLDL secreted by SD rats. Gene expression related to fatty acid and TAG synthesis in ExHC rats was lower than that in SD rats. Enzymatic activities for fatty acid synthesis were also relatively lower in ExHC rats. Moreover, the fatty acid composition of hepatic and serum CE in ExHC rats showed that these CEs were not modified after secretion from the liver despite the similar activities of serum lecithin-cholesterol acyltransferase (LCAT) in ExHC rats to those in SD rats.ConclusionsLow production of liver TAG and secretion of CE-rich, TAG-poor β-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.
Highlights
High serum total cholesterol has been identified as a clinical risk factor for atherosclerosis and cardiovascular disease [1,2]
We have reported that the amount of cholesterol secreted by the liver in Exogenously hypercholesterolemic (ExHC) rats is identical to that secreted by the livers of SD rats [17]
We have previously reported that a high linoleic safflower oil- and cholesterolcontaining diet increases hepatic TAG levels and ameliorates hypercholesterolemia in ExHC rats compared with the effects of an olive oil– and cholesterol-containing diet [35]
Summary
High serum total cholesterol has been identified as a clinical risk factor for atherosclerosis and cardiovascular disease [1,2]. We previously performed linkage analysis adapted to ExHC rats and found Smek as a gene responsible for dietary cholesterol-induced hypercholesterolemia [12]. With this analysis, we established homocongenic Ex.BN-Dihc rats (congenic rats), in which the responsible region for diet-induced hypercholesterolemia on chromosome 14 was recombined to a genome derived from brown Norway (BN) rats. Compared with ExHC rats, congenic rats showed significantly higher hepatic triacylglycerol (TAG) content as well as significantly lower serum cholesterol levels [12]. Hypercholesterolemic (ExHC) rats develop hypercholesterolemia and low hepatic triacylglycerol (TAG) levels when dietary cholesterol is loaded. We compared SD and ExHC rats to investigate a relationship between hypercholesterolemia and the low hepatic TAG levels observed in ExHC rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
