Increased messenger RNA levels for low-density lipoprotein receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase in rat liver after long-term ethanol ingestion.
Because long-term alcohol intake leads to severe alterations of cholesterol metabolism resulting in both elevated serum cholesterol levels and increased hepatic concentrations of cholesterol esters, we investigated the effect of long-term ethanol consumption on the hepatic messenger RNA (mRNA) content of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and low-density lipoprotein receptor, two major regulatory factors in cholesterol metabolism, and of apoprotein E. Twenty-four male Sprague-Dawley rats were pair-fed nutritionally adequate liquid diets containing 36% of total calories as either ethanol or isocaloric carbohydrates for 3 wk. In addition, the lipid content of the diets was varied, resulting in 35%, 17.5%, and 8.8% of total calories corresponding to a daily intake of cholesterol of between 1.2 and 6.3 mg/kg body wt. Although increasing dietary cholesterol intake resulted in a significant decrease of hepatic mRNA for low-density lipoprotein receptor and HMG-CoA reductase (p < 0.05), long-term ethanol consumption led to a significant increase of the mRNA for both proteins (p < 0.01), and this increase was predominantly obvious in animals fed a low-cholesterol diet. In contrast, mRNA content of apoprotein E was found to be significantly lower in livers from rats fed ethanol for a prolonged period of time as compared with controls (p < 0.01), and this effect was found to be still present, although less pronounced, after low cholesterol intake.(ABSTRACT TRUNCATED AT 250 WORDS)
Seitz
H K
HK
Department of Medicine, Salem Medical Center, Heidelberg, Germany.
Kuhn
B
B
von Hodenberg
E
E
Fiehn
W
W
Conradt
C
C
Simanowski
U A
UA
D000284:Administration, Oral; D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D002784:Cholesterol / Q000008:administration & dosage / Q000097:blood / Q000378:metabolism; D002788:Cholesterol Esters / Q000378:metabolism; D000431:Ethanol / Q000008:administration & dosage / Q000633:toxicity*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011973:Receptors, LDL / Q000235:genetics*
D001057:Apolipoproteins E; D002788:Cholesterol Esters; D012333:RNA, Messenger; D011973:Receptors, LDL; D000431:Ethanol; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases