Bröer, AngelikaJuelich, TorstenVanslambrouck, Jessica MTietze, NadineSolomon, Peter SHolst, JeffBailey, Charles G.Rasko, John E JBröer, Stefan2014-08-192014-08-190021-9258http://hdl.handle.net/1885/11954Amino 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 BᴼAT1 (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 BᴼAT1 showed a reduced body weight. When adapted to a standard 20% protein diet, BᴼAT1-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.This work was supported by National Health and Medical Research Council Grant 525415, Australian Research Council Grant DP0877897, University of Sydney Bridging Grant RIMS2009-02579), and by an anonymous foundation14 pages© 2011 by The American Society for Biochemistry and Molecular Biology, IncnutrientsignalingbodyweightcontrolNa⁺neutralaminoacidtransporterSlc6a19BᴼAT1miceintestinekidney2011-07-2910.1074/jbc.M111.2413232015-12-09