Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution
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Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution. / Yap, Yann W; Rusu, Patricia M; Chan, Andrea Y; Fam, Barbara C; Jungmann, Andreas; Solon-Biet, Samantha M; Barlow, Christopher K; Creek, Darren J; Huang, Cheng; Schittenhelm, Ralf B; Morgan, Bruce; Schmoll, Dieter; Kiens, Bente; Piper, Matthew D W; Heikenwälder, Mathias; Simpson, Stephen J; Bröer, Stefan; Andrikopoulos, Sofianos; Müller, Oliver J; Rose, Adam J.
I: Nature Communications, Bind 11, Nr. 1, 2894, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution
AU - Yap, Yann W
AU - Rusu, Patricia M
AU - Chan, Andrea Y
AU - Fam, Barbara C
AU - Jungmann, Andreas
AU - Solon-Biet, Samantha M
AU - Barlow, Christopher K
AU - Creek, Darren J
AU - Huang, Cheng
AU - Schittenhelm, Ralf B
AU - Morgan, Bruce
AU - Schmoll, Dieter
AU - Kiens, Bente
AU - Piper, Matthew D W
AU - Heikenwälder, Mathias
AU - Simpson, Stephen J
AU - Bröer, Stefan
AU - Andrikopoulos, Sofianos
AU - Müller, Oliver J
AU - Rose, Adam J
N1 - CURIS 2020 NEXS 191
PY - 2020
Y1 - 2020
N2 - Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.
AB - Dietary protein dilution (DPD) promotes metabolic-remodelling and -health but the precise nutritional components driving this response remain elusive. Here, by mimicking amino acid (AA) supply from a casein-based diet, we demonstrate that restriction of dietary essential AA (EAA), but not non-EAA, drives the systemic metabolic response to total AA deprivation; independent from dietary carbohydrate supply. Furthermore, systemic deprivation of threonine and tryptophan, independent of total AA supply, are both adequate and necessary to confer the systemic metabolic response to both diet, and genetic AA-transport loss, driven AA restriction. Dietary threonine restriction (DTR) retards the development of obesity-associated metabolic dysfunction. Liver-derived fibroblast growth factor 21 is required for the metabolic remodelling with DTR. Strikingly, hepatocyte-selective establishment of threonine biosynthetic capacity reverses the systemic metabolic response to DTR. Taken together, our studies of mice demonstrate that the restriction of EAA are sufficient and necessary to confer the systemic metabolic effects of DPD.
U2 - 10.1038/s41467-020-16568-z
DO - 10.1038/s41467-020-16568-z
M3 - Journal article
C2 - 32518324
VL - 11
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2894
ER -
ID: 243016879