PMID- 21636576
OWN - NLM
STAT- MEDLINE
DCOM- 20110928
LR  - 20231105
IS  - 1083-351X (Electronic)
IS  - 0021-9258 (Linking)
VI  - 286
IP  - 30
DP  - 2011 Jul 29
TI  - Impaired nutrient signaling and body weight control in a Na+ neutral amino acid 
      cotransporter (Slc6a19)-deficient mouse.
PG  - 26638-51
LID - 10.1074/jbc.M111.241323 [doi]
AB  - Amino acid uptake in the intestine and kidney is mediated by a variety of amino 
      acid transporters. To understand the role of epithelial neutral amino acid uptake 
      in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum 
      neutral (0) amino acid transporter B(0)AT1 (Slc6a19). A general neutral 
      aminoaciduria was observed similar to human Hartnup disorder which is caused by 
      mutations in SLC6A19. Na(+)-dependent uptake of neutral amino acids into the 
      intestine and renal brush-border membrane vesicles was abolished. No compensatory 
      increase of peptide transport or other neutral amino acid transporters was 
      detected. Mice lacking B(0)AT1 showed a reduced body weight. When adapted to a 
      standard 20% protein diet, B(0)AT1-deficient mice lost body weight rapidly on 
      diets containing 6 or 40% protein. Secretion of insulin in response to food 
      ingestion after fasting was blunted. In the intestine, amino acid signaling to 
      the mammalian target of rapamycin (mTOR) pathway was reduced, whereas the 
      GCN2/ATF4 stress response pathway was activated, indicating amino acid 
      deprivation in epithelial cells. The results demonstrate that epithelial amino 
      acid uptake is essential for optimal growth and body weight regulation.
FAU - Broer, Angelika
AU  - Broer A
AD  - Research School of Biology, Australian National University, Canberra, Australian 
      Capital Territory 0200, Australia. Stefan.broer@anu.edu.au
FAU - Juelich, Torsten
AU  - Juelich T
FAU - Vanslambrouck, Jessica M
AU  - Vanslambrouck JM
FAU - Tietze, Nadine
AU  - Tietze N
FAU - Solomon, Peter S
AU  - Solomon PS
FAU - Holst, Jeff
AU  - Holst J
FAU - Bailey, Charles G
AU  - Bailey CG
FAU - Rasko, John E J
AU  - Rasko JE
FAU - Broer, Stefan
AU  - Broer S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110602
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Amino Acid Transport Systems, Neutral)
RN  - 0 (Atf4 protein, mouse)
RN  - 0 (Dietary Proteins)
RN  - 0 (Insulin)
RN  - 0 (SLC6A19 protein, mouse)
RN  - 145891-90-3 (Activating Transcription Factor 4)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Eif2ak4 protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Activating Transcription Factor 4/genetics/metabolism
MH  - Amino Acid Transport Systems, Neutral/genetics/*metabolism
MH  - Animals
MH  - Body Weight/*physiology
MH  - Dietary Proteins
MH  - Eating/*physiology
MH  - Epithelial Cells/*metabolism
MH  - Hartnup Disease/genetics/metabolism
MH  - Humans
MH  - Insulin/genetics/metabolism
MH  - Insulin Secretion
MH  - Mice
MH  - Mice, Mutant Strains
MH  - Mutation
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Signal Transduction/*physiology
MH  - TOR Serine-Threonine Kinases/genetics/metabolism
PMC - PMC3143628
EDAT- 2011/06/04 06:00
MHDA- 2011/09/29 06:00
CRDT- 2011/06/04 06:00
PHST- 2011/06/04 06:00 [entrez]
PHST- 2011/06/04 06:00 [pubmed]
PHST- 2011/09/29 06:00 [medline]
AID - S0021-9258(19)48485-8 [pii]
AID - 10.1074/jbc.M111.241323 [doi]
PST - ppublish
SO  - J Biol Chem. 2011 Jul 29;286(30):26638-51. doi: 10.1074/jbc.M111.241323. Epub 
      2011 Jun 2.