Rate of gastric emptying influences dietary cholesterol absorption efficiency in selected inbred strains of mice

Abstract

Dietary cholesterol contributes ‫ف‬ 50% of the circulating cholesterol in humans and ‫ف‬ 30% of the circulating cholesterol in mice (1, 2). Despite the importance of this process in determining plasma cholesterol level, the mechanisms dictating dietary cholesterol absorption efficiency have not been completely elucidated. This incomplete information is attributable in part to the complexity of the cholesterol absorption process, which involves lipid emulsification in the stomach, lipolytic digestion and bile salt solubilization in the intestinal lumen, enterocyte uptake of the dietary cholesterol, and its assembly into lipoproteins before secretion into the circulation. Thus, differences in the rate and efficiency of each of these processes will contribute to variations in cholesterol absorption efficiency among different individuals.Cholesterol absorption efficiency in humans varies among different individuals even though they may be consuming a similar diet (3-6). Individual differences in cholesterol absorption efficiency were also observed among various inbred strains of rabbits (7,8), rats (9), and mice (10-15). These results suggested a genetic component in the regulation of cholesterol absorption. Early studies on the identification of cholesterol absorption genes have focused on enzymes important for cholesterol ester metabolism in the gastrointestinal tract. Studies with gene knockout mice and specific enzyme inhibitors revealed that both the cholesterol esterification enzyme acyl-CoA:cholesterol acyltransferase and the cholesterol ester hydrolytic enzyme cholesterol esterase modulate the type of intestinal lipoproteins produced (16,17). However, both of these enzymes play only minor roles in determining cholesterol absorption efficiency under normal dietary conditions (16-20). In contrast, enzymes that modulate cholesterol solubility in the intestinal lumen, such as the bile acid synthetic enzymes cholesterol 7 ␣ -hydrolase and sterol 27-hydroxylase, impact cholesterol absorption indirectly by modulating the physical structure of the cholesterol carrier in the intestinal lumen (21,22). More recently, the ATP binding cassette transporter proteins, including ABCA1, ABCG5, and ABCG8, have been implicated as important regulators of dietary cholesterol absorption. These transporters may limit the amount of cholesterol absorbed by enterocytes by catalyzing cholesterol efflux to the intestinal lumen (23-26).Abbreviations: LCT, long-chain triglyceride; l -NAME, N -nitro-l -arginine; MCT, medium-chain triglyceride.

Genetic variation inGlp1rexpression influences the rate of gastric emptying in mice

“…Our evidence for inbred strain differences in gastric emptying rate extends the observations of Kirby et al (24) and provides new information on the identity of candidate genes contributing to this phenotype. Our results are similar in magnitude to those observed between lean and obese humans (13%) (22) and are consistent with the effects of known GLP-1 receptor agonists on food intake and gastric emptying (51).…”

Hypolipidemic Effect of Triphala in Experimentally Induced Hypercholesteremic Rats

“…23) Oral administration of T. chebula reported to increase gastric emptying, might be the reason for decrease in the cholesterol absorption. 24) Drugs like Statins administration results in reduction of LDL cholesterol by inhibiting HMG-CoA reductase in the liver. In our study, we have observed reduction in the LDL cholesterol in hyperlipidimic rats after Triphala administration.…”

Differing rates of cholesterol absorption among inbred mouse strains yield differing levels of HDL-cholesterol

“…Although Wang, Paigen, and Carey ( 17 ) have shown that cholesterol absorption effi ciencies are not determined by intestinal transit times, Kirby, Howles, and Hui ( 25 ) have shown that differences in cholesterol absorption in SJL/J and 129 mice are attributable to differences in the rate of gastric emptying. In that study, the 129 mice have a slower rate of gastric emptying and a slower appearance of cholesterol in the plasma, similar to what we see with the C57 mice.…”

“…Additionally, the ATP binding cassette transporter proteins ABCG5 and ABCG8 have been shown to be involved in resecretion of the enterocyte cholesterol back into the lumen ( 23,24 ). Other factors, including the rate of gastric emptying, have been shown to alter the rate of cholesterol absorption between inbred mouse strains ( 25 ).…”