Proline Absorption and SGK1 Expression are Inhibited in Intestinal Tis7 Transgenic Mice

Abstract

Background/Aims: Expression of the transcriptional co-regulator tis7 is markedly increased in the adaptive small intestine in a mouse model of short bowel syndrome. Transgenic mice with enterocytic overexpression of tis7 (tis7^tg) have accelerated triglyceride absorption, with increased adiposity yet reduced skeletal muscle mass. To further explore this phenotype, we examined whether tis7 also regulates amino acid and carbohydrate absorption. Methods: Small intestinal glucose and amino acid uptake were quantified in wild type (WT) and tis7^tg mice. Amino acid transporter expression was assessed by qRT-PCR and immunoblot. Apical cell surface transporter expression was quantified by cell surface biotinylation. Results: Active glucose uptake rates were unchanged. Uptake of proline but not leucine was significantly reduced in tis7^tg vs. WT jejunum. Expression of serum and glucocorticoid-induced kinase 1 (SGK1), a solute carrier activator, was inhibited in tis7^tg jejunum. Apical membrane expression of the proline transporter SLC6A20 was reduced in tis7^tg jejunum. Conclusions: Tis7 overexpression in enterocytes inhibits proline uptake, associated with decreased expression of activated SGK1 and reduced cell surface expression of SLC6A20. Consistent with the observed tis7^tg phenotype, tis7 overexpression increases triglyceride absorption but has adverse effects on the uptake of selected amino acids. Tis7 has pleiotropic effects on nutrient absorption.