title: Proline Absorption and SGK1 Expression are Inhibited in Intestinal Tis7 Transgenic Mice.
abstract: OBJECTIVE
  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 (tis7tg) 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 tis7tg 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 tis7tg vs. WT jejunum. Expression of serum and glucocorticoid-induced kinase 1 (SGK1), a solute carrier activator, was inhibited in tis7tg jejunum. Apical membrane expression of the proline transporter SLC6A20 was reduced in tis7tg 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 tis7tg phenotype, tis7 overexpression increases triglyceride absorption but has adverse effects on the uptake of selected amino acids. Tis7 has pleiotropic effects on nutrient absorption.
authors.forename: Jianyun
authors.initials: J
authors.lastname: Lu
authors.forename: Amy M
authors.initials: AM
authors.lastname: Garcia
authors.forename: Taylor
authors.initials: T
authors.lastname: Geisman
authors.forename: Derek
authors.initials: D
authors.lastname: Wakeman
authors.forename: Brad W
authors.initials: BW
authors.lastname: Warner
authors.forename: Elzbieta A
authors.initials: EA
authors.lastname: Swietlicki
authors.forename: Marc S
authors.initials: MS
authors.lastname: Levin
authors.forename: Deborah C
authors.initials: DC
authors.lastname: Rubin
mesh_terms: D026905:Amino Acid Transport Systems / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D001835:Body Weight; D059305:Diet, High-Fat; D005947:Glucose / Q000378:metabolism; D017874:Immediate-Early Proteins / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D007583:Jejunum / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D010766:Phosphorylation; D011392:Proline / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D026905:Amino Acid Transport Systems; D005947:Glucose; D017874:Immediate-Early Proteins; D008565:Membrane Proteins; D011392:Proline; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D000099184:Serum-Glucocorticoid Regulated Kinases; C490044:Ifrd1 protein, mouse; C000588564:Slc6a20a protein, mouse