Dietary calcium decreases plasma cholesterol by down-regulation of intestinal Niemann-Pick C1 like 1 and microsomal triacylglycerol transport protein and up-regulation of CYP7A1 and ABCG 5/8 in hamsters

Scope: It has been shown that calcium supplementation favorably modifies plasma lipoprotein profile in postmenopausal women. The present study investigated the interaction of dietary calcium with genes of transporters, receptors and enzymes involved in cholesterol metabolism. Methods and results: Forty-eight ovariectomized hamsters were fed one of the four diets containing 0, 2, 6 and 8 g calcium per kg. Plasma total cholesterol (TC), triacylglycerols (TG), and non-high density lipoprotein cholesterol were dose-dependently decreased, whereas high-density lipoprotein cholesterol (HDL-C) was dose-dependently increased with the increasing dietary calcium levels. Dietary calcium had no effect on protein mass of hepatic sterol regulatory element binding protein-2 (SREBP), liver X receptor-alpha (LXR), 3-hydroxy-3-methylglutaryl-CoA reductase (HMGR), LDL receptor (LDLR) and cholesterol-7 alpha-hydroxylase (CYP7A1). However, dietary calcium up-regulated the mRNA levels of hepatic CYP7A1 and intestinal ATP binding cassette transporters (ABCG5/8) whereas it down-regulated the intestinal Niemann-Pick C1 like 1 (NPC1L1) and microsomal triacylglycerol transport protein (MTP). In addition, dietary calcium increased the activity of intestinal acyl coenzyme A: cholesterol acyltransferase 2, while it decreased plasma cholesteryl ester transport protein (CETP). Conclusion: Beneficial modification of lipoprotein profile by dietary calcium was mediated by sequestering bile acid absorption and enhancing excretion of fecal cholesterol, via up-regulation of mRNA CYP7A1 and intestinal ABCG 5/8 with down-regulation of mRNA NPC1L1 and MTP.