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Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.

ABSTRACT: 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.

SUBMITTER: Yap YW

PROVIDER: S-EPMC7283339 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Restriction of essential amino acids dictates the systemic metabolic response to dietary protein dilution.

Yap Yann W YW Rusu Patricia M PM Chan Andrea Y AY Fam Barbara C BC Jungmann Andreas A Solon-Biet Samantha M SM Barlow Christopher K CK Creek Darren J DJ Huang Cheng C Schittenhelm Ralf B RB Morgan Bruce B Schmoll Dieter D Kiens Bente B Piper Matthew D W MDW Heikenwälder Mathias M Simpson Stephen J SJ Bröer Stefan S Andrikopoulos Sofianos S Müller Oliver J OJ Rose Adam J AJ

Nature communications 20200609 1

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 supp ...[more]

PMID: 32518324

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Project description:Free amino acids in the phloem sap are the dominant nitrogen source for aphids, but their availability is usually poor. Although some studies have explored the effect of dietary amino acid restriction on aphid performance, little is known about the molecular basis of these effects. Here, we examined the performance and transcriptome of the green peach aphid, Myzus persicae, fed a standard diet (Control diet) or a diet containing 50% of the total amino acids of the Control diet (Half diet). Aphid weight and fecundity were significantly reduced in the Half diet group. Transcriptomic analysis showed that a total of 1460 genes were differentially expressed between the groups were fed on the two diets, which many of them were associated with nutrient and energy metabolism. When feeding on the Half diet, aphids upregulated genes associated with the amino acid biosynthetic pathway (predominantly amino acid biosynthesis genes and some amino acid transporter genes) as well as the cysteine and serine protease genes. Furthermore, these aphids displayed increased expression of genes associated with glycolysis, which could generate intermediates for de novo amino acid biosynthesis. Consistent with this, elevated glucose levels were observed in aphids in the Half diet group. Additionally, the expression levels of several genes associated with hormonal signaling pathway were altered. Several genes related to juvenile hormone and insulin-like peptide (ILP) signaling were downregulated, including Krüppel homolog 1 (Kr-h1) and insulin-like peptide 5 (Ilp5), respectively. In contrast, several genes related to ecdysone signaling were upregulated including broad-complex core protein (Br-c) and shade (Shd). Despite their poor performances, M. persicae adapted to dietary restriction of amino acids, through upregulation of genes involved in amino acid biosynthesis, glycolysis, and protein degradation, as well as by altering the expression level of genes involved in hormone signaling pathways.

Project description:Reproductive functions are regulated by the sophisticated coordination between the neuronal and endocrine systems and are sustained by a proper nutritional environment. Female reproductive function is vulnerable to effects from dietary restrictions, suggesting a transient adaptation that prioritizes individual survival over reproduction until a possible future opportunity for satiation. This adaptation could also partially explain the existence of amenorrhea in women with anorexia nervosa. Because amino acid nutritional conditions other than caloric restriction uniquely alters amino acid metabolism and affect the hormonal levels of organisms, we hypothesized that the supply of essential amino acids in the diet plays a pivotal role in the maintenance of the female reproductive system. To test this hypothesis, we examined ovulatory cyclicity in female rats under diets that were deficient in threonine, lysine, tryptophan, methionine or valine. Ovulatory cyclicity was monitored by daily cytological evaluations of vaginal smears. After continuous feeding of the deficient diet, a persistent diestrus or anovulatory state was induced most quickly by the valine-deficient diet and most slowly by the lysine-deficient diet. A decline in the systemic insulin-like growth factor 1 level was associated with a dietary amino acid deficiency. Furthermore, a paired group of rats that were fed an isocaloric diet with balanced amino acids maintained normal estrous cyclicity. These disturbances of the estrous cycle by amino acid deficiency were quickly reversed by the consumption of a normal diet. The continuous anovulatory state in this study is not attributable to a decrease in caloric intake but to an imbalance in the dietary amino acid composition. With a shortage of well-balanced amino acid sources, reproduction becomes risky for both the mother and the fetus. It could be viewed as an adaptation to the diet, diverting resources away from reproduction and reallocating them to survival until well-balanced amino acid sources are found.

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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.

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