Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution
| Autor: | Stefan Bröer, Christopher K. Barlow, Cheng Huang, Stephen J. Simpson, Darren J. Creek, Dieter Schmoll, Matthew D.W. Piper, Andrea Y. Chan, Samantha M. Solon-Biet, Bente Kiens, Oliver J. Müller, Yann W. Yap, Adam J. Rose, Barbara C Fam, Bruce A. Morgan, Mathias Heikenwalder, Andreas Jungmann, Patricia M. Rusu, Ralf B. Schittenhelm, Sofianos Andrikopoulos |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Male
Threonine 0301 basic medicine medicine.medical_specialty FGF21 Science General Physics and Astronomy 030209 endocrinology & metabolism Article General Biochemistry Genetics and Molecular Biology Gastrointestinal Hormones Mice 03 medical and health sciences 0302 clinical medicine Casein Internal medicine medicine Metabolome Animals Homeostasis Obesity lcsh:Science chemistry.chemical_classification Multidisciplinary Tryptophan Lipid metabolism General Chemistry Animal Feed Amino acid Fibroblast Growth Factors Mice Inbred C57BL Proteinuria Phenotype 030104 developmental biology Endocrinology Liver chemistry Hepatocytes Female lcsh:Q Amino Acids Essential Dietary Proteins |
| Zdroj: | Yap, Y W, Rusu, P M, Chan, A Y, Fam, B C, Jungmann, A, Solon-Biet, S M, Barlow, C K, Creek, D J, Huang, C, Schittenhelm, R B, Morgan, B, Schmoll, D, Kiens, B, Piper, M D W, Heikenwälder, M, Simpson, S J, Bröer, S, Andrikopoulos, S, Müller, O J & Rose, A J 2020, ' Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution ', Nature Communications, vol. 11, no. 1, 2894 . https://doi.org/10.1038/s41467-020-16568-z Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| Popis: | 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. Dietary protein dilution, where protein is reduced and replaced by other nutrient sources without caloric restriction, promotes metabolic health via the hepatokine Fgf21. Here, the authors show that essential amino acids threonine and tryptophan are necessary and sufficient to induce these effects. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|