Transporters for the Intestinal Absorption of Cholesterol, Vitamin E, and Vitamin K

Abstract

Humans cannot synthesize fat-soluble vitamins such as vitamin E and vitamin K. For this reason, they must be obtained from the diet via intestinal absorption. As the deficiency or excess of these vitamins has been reported to cause several types of diseases and disorders in humans, the intestinal absorption of these nutrients must be properly regulated to ensure good health. However, the mechanism of their intestinal absorption remains poorly understood. Recent studies on cholesterol using genome-edited mice, genome-wide association approaches, gene mutation analyses, and the development of cholesterol absorption inhibitors have revealed that several membrane proteins play crucial roles in the intestinal absorption of cholesterol. Surprisingly, detailed analyses of these cholesterol transporters have revealed that they can also transport vitamin E and vitamin K, providing clues to uncover the molecular mechanisms underlying the intestinal absorption of these fat-soluble vitamins. In this review, we focus on the membrane proteins (Niemann-Pick C1 like 1, scavenger receptor class B type I, cluster of differentiation 36, and ATP-binding cassette transporter A1) that are (potentially) involved in the intestinal absorption of cholesterol, vitamin E, and vitamin K and discuss their physiological and pharmacological importance. We also discuss the related uncertainties that need to be explored in future studies.

Beneficial Effect of Ezetimibe on Cholesterol Metabolism Ameliorates Hepatic Steatosis

“…[18,19,29] Recent studies have shown that ezetimibe efficiently reduces the absorption of dietary and biliary cholesterol in the proximal jejunum and inhibits the transport of serum cholesterol to liver by binding to Niemann-Pick C1-like 1 (NPCL1) sterol transporter in the enterocyte brush border membrane and hepatocyte canalicular membrane. [36,37] In humans, NPCL1 protein is expressed predominantly in the liver and to a lesser extent in the intestine. [19] Thus, the heretofore demonstrated anti-steatosis activity of ezetimibe plus the results of the present meta-analysis underscore the promise of ezetimibe for ameliorating hepatic steatosis.…”

Microbial Metabolites and Intestinal Stem Cells Tune Intestinal Homeostasis

“…[ 153,154 ] Although these vitamins can be obtained from the diet, the presence of specific transporters for these vitamins in colonocytes suggests an important role for gut microbes to regulate vitamin availability during homeostasis. [ 153,155 ] The effect of gut microbiota‐derived vitamins on cellular growth is universally accepted; [ 153 ] nevertheless, only a handful of studies have focused on their role on intestinal stem cells. Bashir et al.…”

Gall bladder: The metabolic orchestrator

“…Following food intake, the GB bile is released into the duodenum. Together with dietary cholesterol, biliary cholesterol is absorbed by the enterocytes through sterol transporters such as Niemann‐Pick C1 Like 1, cluster of differentiation 36, scavenger receptor class B type I, and ATP‐binding cassette transporter A1 . Genetic polymorphisms of genes encoding these transporters could therefore disturb the delicate balance between cholesterol secretion and absorption, resulting in gallstone formation and metabolic dysregulation .…”