Proline absorption and SGK1 expression are inhibited in intestinal Tis7 transgenic mice

Jianyun Lu, Amy M. Garcia, Taylor Geisman, Derek Wakeman, Brad W. Warner, Elzbieta A. Swietlicki, Marc S. Levin, Deborah C. Rubin

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish
Pages (from-to)1532-1543
Number of pages12
JournalCellular Physiology and Biochemistry
Volume38
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Adaptation
  • Amino acid absorption
  • Intestine
  • Short bowel syndrome
  • Tis7/IFRD1

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