Genes that affect cholesterol synthesis, cholesterol absorption, and chylomicron assembly: the relationship between the liver and intestine in control and streptozotosin diabetic rats.
Chylomicrons and very low-density lipoproteins (VLDLs) are abnormal in diabetes. The aim of this study was to compare the expression of Niemann-Pick C1-like1 (NPC1L1), adenosine triphosphate-binding cassette (ABC) proteins G5 and G8, microsomal triglyceride transfer protein (MTP), and 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase in the fasting and fed states in nondiabetic Sprague-Dawley rats fed a high-fat/cholesterol diet and to examine the messenger RNA (mRNA) expression of these proteins in the liver and intestine of diabetic and control animals using streptozotosin diabetic cholesterol-fed rats. Chylomicron and VLDL concentrations were significantly lower after a 12-hour fast in fasted compared with fed rats (P < .02). There was no change with fasting in mRNA expression of any of the genes in the intestine, but MTP level was significantly lower in the liver after the 12-hour fast (P < .01). There was a positive correlation between intestinal NPC1L1 mRNA and chylomicron cholesterol (P < .01) and between hepatic NPC1L1 mRNA and VLDL cholesterol (P < .01). The diabetic rats had significantly higher chylomicron and VLDL cholesterol, triglyceride, and apolipoprotein B-48 and B-100 levels compared with control rats (P < .0001). They had significantly increased NPC1L1 and MTP mRNA in both liver and intestine (P < .05 and P < .0005, respectively), and ABCG5 and ABCG8 mRNA were significantly reduced (P < .05). HMGCoA reductase mRNA was increased in diabetic animals (P < .01). In conclusion, fasting intestinal gene expression reflects the fed state. In diabetes, intestinal and hepatic gene expression correlates with abnormalities in chylomicron and VLDL cholesterol.
Lally
Sean
S
Department of Diabetes and Endocrinology, Trinity College, Dublin 18, Ireland.
Owens
Daphne
D
Tomkin
Gerald H
GH
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000042:Absorption; D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002914:Chylomicrons / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism*; D008074:Lipoproteins / Q000235:genetics; D008079:Lipoproteins, VLDL / Q000097:blood; D008099:Liver / Q000378:metabolism*; D026901:Membrane Transport Proteins / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013311:Streptozocin
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D000071019:ATP Binding Cassette Transporter, Subfamily G, Member 8; D018528:ATP-Binding Cassette Transporters; C480692:Abcg5 protein, rat; C480693:Abcg8 protein, rat; D002914:Chylomicrons; D008074:Lipoproteins; D008079:Lipoproteins, VLDL; D026901:Membrane Transport Proteins; C482444:NPC1L1 protein, rat; D012333:RNA, Messenger; D013311:Streptozocin; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases