Regulation of the expression of carbohydrate digestion/absorption-related genes

Br J Nutr. 2000 Dec;84 Suppl 2:S245-8. doi: 10.1079/096582197388626.

Abstract

To explore the underlying molecular mechanism whereby nutrients modulate the expression of intestinal digestion/absorption-related genes, we have cloned the 5' flanking regions of two representing disaccharidase genes, i.e. sucrase-isomaltase (SI) and lactase-phlorizin hydrolase (LPH), and investigated whether the binding activity of putative common nuclear factor(s) binding to the cis-elements located in these regions is altered by dietary manipulations. Oro-gastric feeding of a sucrose-containing diet to rats caused parallel increases in SI mRNA and LPH mRNA levels within 3 h. Among the monosaccharides tested, fructose gave rise to the most prominent increase in the mRNA levels of SI and LPH genes, which were accompanied by a coordinate rise in the mRNA levels of two microvillar hexose transporters, i.e. SGLT1 and GLUT5. Nuclear run-on assays revealed that fructose, but not glucose, increased the transcription of SI, LPH and GLUT5. DNase I footprinting analysis of the rat LPH gene showed that the protected region conserved the same sequence as the cis-element (CE-LPH1) reported in the pig LPH gene. Electrophoretic mobility shift assay using CE-LPH1 and the related cis-element of SI gene (SIF1) revealed that nuclear extracts from the jejunum of rats fed the high-starch diet gave greater density of retarded bands than those of rats fed the low-starch diet. Force feeding a fructose diet gave rise to an increase in the binding of the dimeric nuclear protein (Cdx-2) to the SIF1 element. These results suggest that the cis-elements of CE-LPH1 and SIF1 might be involved in the carbohydrate-induced increases of the transcription of LPH and SI, presumably through a change in the expression and/or binding activity of Cdx-2.

MeSH terms

  • Animals
  • CDX2 Transcription Factor
  • Dietary Carbohydrates / administration & dosage
  • Dietary Carbohydrates / metabolism*
  • Digestion / genetics*
  • Fructose / metabolism
  • Gene Expression Regulation / physiology*
  • Glucose Transporter Type 5
  • Homeodomain Proteins / metabolism*
  • Intestinal Absorption / genetics*
  • Intestine, Small / metabolism*
  • Lactase-Phlorizin Hydrolase / genetics
  • Monosaccharide Transport Proteins / genetics
  • RNA, Messenger / metabolism
  • Rats
  • Sucrase-Isomaltase Complex / genetics
  • Trans-Activators
  • Transcription, Genetic

Substances

  • CDX2 Transcription Factor
  • Dietary Carbohydrates
  • Glucose Transporter Type 5
  • Homeodomain Proteins
  • Monosaccharide Transport Proteins
  • RNA, Messenger
  • Trans-Activators
  • Fructose
  • Sucrase-Isomaltase Complex
  • Lactase-Phlorizin Hydrolase