Abstract
There is increasing evidence that the magnitude and potential of intestinal nutrient
absorption (sugars, fatty acids, cholesterol and triglycerides) and intestinal defense
function are regulated by metabolic learning phenomena, and are influenced by dietary
energy content and exercise. Metabolic overload syndromes, mainly obesity, and chronic
malabsorption disorders such as inflammatory bowel disease and celiac disease have
been defined as extreme phenotypes. Metabolic learning processes depend on developmental
and transcriptional control systems of intestinal epithelial cell differentiation.
The physiological differentiation zone of enterocytes is linked to the beta-catenin
system, apolipoprotein apoA-IV and the master transcription factors Cdx2, HNF1α, and
GATA4. In addition to these developmental regulatory transcription factors, nuclear
receptors including RXR, LXR, PPAR, PXR, and CAR have been implicated in the generation
of more absorptive enterocytes with a more differentiated phenotype on the one hand,
and dedifferentiated cells with reduced capacity of detoxification and defense causing
loss of junction control and barrier defects on the other. Large-scale analysis of
gene expression profiles and identification of key pathways and master regulatory
transcription factors will help dissect the role of nutritional and environmental
factors as well as pharmacological intervention on mucosal homeostasis and disease,
with potential applications for diagnosis and therapy.
Key words
Metabolic learning - intestine
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Correspondence
Gerd Schmitz
Institute of Clinical Chemistry·University of Regensburg
Franz-Josef-Strauss-Allee 11·93042 Regensburg·Germany
Phone: +49/941/944-62 01
Fax: +49/941/944-62 02
Email: gerd.schmitz@klinik.uni-regensburg.de