Frequent Cholesterol Intake Up-regulates Intestinal NPC1L1, ACAT2, and MTP

Abstract

Dietary cholesterol elevates plasma total cholesterol (TC) level. However, no study to date has examined how cholesterol intake frequency interacts with the gene of sterol transporters, receptors, and enzymes involved in cholesterol metabolism. Thirty-three hamsters were divided into three groups with the control hamsters being given daily 9 mg of cholesterol in the diet (CD), whereas the second group being gavage-administered 3 mg of cholesterol three times per day (C-3) and the third group being gavage-administered 9 mg of cholesterol one time per day (C-1). The experiment lasted for 6 weeks. The hamsters were killed under carbon dioxide suffocation. Data demonstrated that plasma TC, non-high-density lipoprotein cholesterol, and triacylglycerols were elevated with the increasing cholesterol intake frequency. Western blotting analyses revealed that the intake frequency had no effect on protein mass of hepatic sterol regulatory element binding protein-2, liver X receptor-alpha, 3-hydroxy-3-methylglutaryl-CoA reductase, LDL receptor, and cholesterol-7alpha-hydroxylase. However, the frequent cholesterol intake down-regulated the mRNA level of hepatic LDL receptor. In contrast, the frequent cholesterol intake up-regulated the mRNA levels of intestinal Niemann-Pick C1-like 1 (NPC1L1), acyl coenzyme A:cholesterol acyltransferase 2 (ACAT2), and microsomal triacylglycerol transport protein (MTP). It was concluded that the cholesterol intake frequency-induced elevation in plasma TC was associated with greater cholesterol absorption, possibly mediated by up-regulation of NPC1L1, ACAT2, and MTP.