RRC ID 33265
Author Tanaka Y, Nagao K, Nakagiri H, Nagaso T, Iwasa Y, Mori H, Asahina M, Imaizumi K, Sato M.
Title Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats.
Journal Lipids Health Dis
Abstract 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 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.
CONCLUSIONS:Low 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.
Volume 13
Pages 19
Published 2014-1-22
DOI 10.1186/1476-511X-13-19
PII 1476-511X-13-19
PMID 24450544
PMC PMC3902423
MeSH Animals Biosynthetic Pathways Cholesterol Esters / blood* Cholesterol, Dietary / adverse effects* Diet, High-Fat / adverse effects Fatty Acids / blood Golgi Apparatus / metabolism Hypercholesterolemia / blood* Hypercholesterolemia / etiology Lipid Metabolism Liver / metabolism* Male Phosphatidylcholine-Sterol O-Acyltransferase / blood RNA, Messenger / genetics RNA, Messenger / metabolism Rats Rats, Sprague-Dawley Transcriptome Triglycerides / metabolism*
IF 2.906
Times Cited 2
Rats ExHC/Seac