Impaired nutrient signaling and body weight control in a Na⁺ neutral amino acid cotransporter (Slc6a19)-deficient mouse
Date
2011-07-29
Authors
Bröer, Angelika
Juelich, Torsten
Vanslambrouck, Jessica M
Tietze, Nadine
Solomon, Peter S
Holst, Jeff
Bailey, Charles G.
Rasko, John E J
Bröer, Stefan
Journal Title
Journal ISSN
Volume Title
Publisher
American Society for Biochemistry and Molecular Biology
Abstract
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 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.
Description
Keywords
nutrient, signaling, body, weight, control, Na⁺, neutral, amino, acid, transporter, Slc6a19, BᴼAT1, mice, intestine, kidney
Citation
Collections
Source
Journal of biological chemistry 286. 30 (2011): 26638-26651
Type
Journal article