Unavailability of liver triacylglycerol increases serum cholesterol concentration induced by dietary cholesterol in exogenously hypercholesterolemic (ExHC) rats.
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.
Yasutake
Y
Tanaka
Koji
K
Nagao
Hideaki
H
Nakagiri
Toshirou
T
Nagaso
Yasue
Y
Iwasa
Haruhiko
H
Mori
Makoto
M
Asahina
Katsumi
K
Imaizumi
Laboratory of Nutrition Chemistry, Division of Bioresource and Bioenvironmental Sciences, Graduate School, Kyushu University, 6-10-1 hakozaki, higashi-ku, Fukuoka 812-8581, Japan. masaos@agr.kyushu-u.ac.jp.
Masao
M
Sato
D000818:Animals; D053898:Biosynthetic Pathways; D002788:Cholesterol Esters / Q000097:blood*; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D059305:Diet, High-Fat / Q000009:adverse effects; D005227:Fatty Acids / Q000097:blood; D006056:Golgi Apparatus / Q000378:metabolism; D006937:Hypercholesterolemia / Q000097:blood* / Q000209:etiology; D050356:Lipid Metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D007862:Phosphatidylcholine-Sterol O-Acyltransferase / Q000097:blood; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D059467:Transcriptome; D014280:Triglycerides / Q000378:metabolism*
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D005227:Fatty Acids; D012333:RNA, Messenger; D014280:Triglycerides; D007862:Phosphatidylcholine-Sterol O-Acyltransferase