Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats

作者：Tanaka Yasutake; Nagao Koji; Nakagiri Hideaki; Nagaso Toshirou; Iwasa Yasue; Mori Haruhiko; Asahina Makoto; Imaizumi Katsumi; Sato Masao^*

来源：Lipids in Health and Disease, 2014, 13(1): 19.

DOI：10.1186/1476-511X-13-19

• Hypercholesterolemia
• ExHC rats
• Triacylglycerol
• Fatty acid synthase
• Golgi apparatus
• beta-VLDL

Background: Exogenously 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. Methods: Male 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. Results: We 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 beta-very-low-density lipoprotein (beta-VLDL) that had higher cholesterol ester (CE) and lower TAG content than those in the beta-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. Conclusions: Low production of liver TAG and secretion of CE-rich, TAG-poor beta-VLDL without modification by LCAT in the circulation contributed to hypercholesterolemia induced by dietary cholesterol in ExHC rats.

• 出版日期2014-1-22