Genes that affect cholesterol synthesis, cholesterol absorption, and chylomicron assembly: The relationship between the liver and intestine in control and streptozotosin diabetic rats

Abstract

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.