scholarly journals Compositional and Functional Adaptations of Intestinal Microbiota and Related Metabolites in CKD Patients Receiving Dietary Protein Restriction

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2799
Author(s):  
I-Wen Wu ◽  
Chin-Chan Lee ◽  
Heng-Jung Hsu ◽  
Chiao-Yin Sun ◽  
Yuen-Chan Chen ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Dietary Protein ◽  
Serum Levels ◽  
Protein Restriction ◽  
Protein Diet ◽  
Secondary Bile Acid ◽  
Bacterial Gene ◽  
Dietary Protein Restriction ◽  
The Relationship ◽  
Serum Metabolomics

The relationship between change of gut microbiota and host serum metabolomics associated with low protein diet (LPD) has been unraveled incompletely in CKD patients. Fecal 16S rRNA gene sequencing and serum metabolomics profiling were performed. We reported significant changes in the β-diversity of gut microbiota in CKD patients having LPD (CKD-LPD, n = 16). We identified 19 genera and 12 species with significant differences in their relative abundance among CKD-LPD patients compared to patients receiving normal protein diet (CKD-NPD, n = 27) or non-CKD controls (n = 34), respectively. CKD-LPD had a significant decrease in the abundance of many butyrate-producing bacteria (family Lachnospiraceae and Bacteroidaceae) associated with enrichment of functional module of butanoate metabolism, leading to concomitant reduction in serum levels of SCFA (acetic, heptanoic and nonanoic acid). A secondary bile acid, glyco λ-muricholic acid, was significantly increased in CKD-LPD patients. Serum levels of indoxyl sulfate and p-cresyl sulfate did not differ among groups. The relationship between abundances of microbes and metabolites remained significant in subset of resampling subjects of comparable characteristics. Enrichment of bacterial gene markers related to D-alanine, ketone bodies and glutathione metabolism was noted in CKD-LPD patients. Our analyses reveal signatures and functions of gut microbiota to adapt dietary protein restriction in renal patients.

scholarly journals Proximal tubule glutamine synthetase expression is necessary for the normal response to dietary protein restriction

2017 ◽  
Vol 313 (1) ◽  
pp. F116-F125 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Gunars Osis ◽  
Mary E. Handlogten ◽  
Jill W. Verlander ◽  
I. David Weiner
Keyword(s):  
Glutamine Synthetase ◽  
Proximal Tubule ◽  
Dietary Protein ◽  
Acid Production ◽  
Protein Intake ◽  
Ammonia Excretion ◽  
Protein Restriction ◽  
Protein Diet ◽  
Acid Excretion ◽  
Dietary Protein Restriction

Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion changes in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of [Formula: see text] and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation. Because renal proximal tubule GS expression increases during dietary protein restriction, this could contribute to the decreased ammonia excretion. The purpose of the current study was to determine the role of proximal tubule GS in the renal response to protein restriction. We generated mice with proximal tubule-specific GS deletion (PT-GS-KO) using Cre-loxP techniques. Cre-negative (Control) and PT-GS-KO mice in metabolic cages were provided 20% protein diet for 2 days and were then changed to low-protein (6%) diet for the next 7 days. Additional PT-GS-KO mice were maintained on 20% protein diet. Dietary protein restriction caused a rapid decrease in urinary ammonia excretion in both genotypes, but PT-GS-KO blunted this adaptive response significantly. This occurred despite no significant genotype-dependent differences in urinary pH or in serum electrolytes. There were no significant differences between Control and PT-GS-KO mice in expression of multiple other proteins involved in renal ammonia handling. We conclude that proximal tubule GS expression is necessary for the appropriate decrease in ammonia excretion during dietary protein restriction.

Effect of Dietary Protein Restriction on Renal Purines and Purine-Metabolizing Enzymes in Adriamycin Nephrosis in Rats: A Mechanism for Protection against Acute Proteinuria Involving Xanthine Oxidase Inhibition

1990 ◽  
Vol 79 (6) ◽  
pp. 647-656 ◽  
Author(s):  
Gian Marco Ghiggeri ◽  
Fabrizio Ginevri ◽  
Giovanni Cercignani ◽  
Roberta Oleggini ◽  
Alessando Garberi ◽  
...  
Keyword(s):  
Xanthine Oxidase ◽  
Dietary Protein ◽  
Purine Nucleoside Phosphorylase ◽  
Protein Restriction ◽  
Purine Nucleoside ◽  
Protein Diet ◽  
Low Protein Diet ◽  
Dietary Protein Restriction ◽  
Low Protein ◽  
Normal Protein Diet

1. A low protein diet prevents the development of proteinuria and glomerular damage in adriamycin experimental nephrosis without affecting renal haemodynamics. In this study the hypothesis was tested as to whether protein restriction is able to modulate the purine metabolic cycle and related enzymes such as xanthine oxidase, one of the putative effectors of adriamycin nephrotoxicity. 2. Renal activities of xanthine oxidase and purine nucleoside phosphorylase were markedly depressed in adriamycin-treated rats fed a 9% casein (low protein) diet compared with the group fed a 22% casein (normal protein) diet both 1 day after adriamycin administration and at the time of appearance of heavy proteinuria (day 15), whereas the activity of renal adenosine deaminase was unchanged. 3. The concentrations of the metabolic substrates of xanthine oxidase, i.e. hypoxanthine and xanthine, were constantly lower in renal homogenates of rats fed a low protein diet compared with those on a normal protein diet. In urine, uric acid, the product of hypoxanthine-xanthine transformation, was lower 1 day after adriamycin injection in protein-restricted rats compared with the group on a normal protein diet which showed a marked increase in its excretion. At the same time, the urinary efflux of adenosine 5′-monophosphate, which is the precursor nucleotide of the above-mentioned nucleosides and bases, was very high in rats fed a low protein diet, whereas it was absent in the group on a normal protein diet. 4. The progressive increment in proteinuria of glomerular origin (i.e. increased excretion of albumin and transferrin) typical of adriamycin-treated rats fed a normal protein diet was inhibited in the protein-restricted animals, which were normoproteinuric on day 10 and were only slightly proteinuric on day 15. 5. Like protein restriction, the pharmacological suppression of renal xanthine oxidase by dietary tungstate and the scavenging by dimethylthiourea of the putative free radical deriving from the action of xanthine oxidase, were associated with a similar (quantitative and qualitative) inhibition of glomerular proteinurea. 6. These data demonstrate that dietary protein restriction is associated with a block in purine metabolism within the kidney due to a marked reduction in the activities of two main enzymes of the cycle, i.e. purine nucleoside phosphorylase and xanthine oxidase, the latter being a putative effector of adriamycin nephrotoxicity. The partial reduction of proteinuria induced by a low protein diet is quantitatively and qualitatively comparable with the reduction induced by the specific block of renal xanthine oxidase or by the scavenging of OH · deriving from hypoxanthine and xanthine transformation. The crucial factor(s) determining protection against proteinuria in adriamycin nephrosis may be decreased xanthine oxidase activity in the kidney and inhibition of the O2 · and OH · production via the xanthine oxidase system.

Role of FGF21 and GCN2 in mediating the metabolic response to dietary protein restriction

2016 ◽  
Vol 11 (S 01) ◽  
Author(s):  
T Laeger ◽  
DC Albarado ◽  
L Trosclair ◽  
J Hedgepeth ◽  
CD Morrison
Keyword(s):  
Dietary Protein ◽  
Metabolic Response ◽  
Protein Restriction ◽  
Dietary Protein Restriction

Neuronal FGF-21 Signaling–A Sensor of Dietary Protein Restriction

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 261-LB
Author(s):  
CRISTAL M. HILL ◽  
MADELEINE V. DEHNER ◽  
DAVID MCDOUGAL ◽  
HANS-RUDOLF BERTHOUD ◽  
HEIKE MUENZBERG ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Protein Restriction ◽  
Dietary Protein Restriction

238-LB: Dietary Protein Restriction Induces Myocardial Dysfunction Despite Reducing Body Weight in Aged C57BL/6J Mice

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 238-LB
Author(s):  
CHRISTOPHER L. AXELROD ◽  
WAGNER S. DANTAS ◽  
GANGARAO DAVULURI ◽  
WILLIAM T. KING ◽  
CRISTAL M. HILL ◽  
...  
Keyword(s):  
Body Weight ◽  
Dietary Protein ◽  
Myocardial Dysfunction ◽  
Protein Restriction ◽  
Dietary Protein Restriction

scholarly journals The Role of Reduced Methionine in Mediating the Metabolic Responses to Protein Restriction Using Different Sources of Protein

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2609
Author(s):  
Han Fang ◽  
Kirsten P. Stone ◽  
Sujoy Ghosh ◽  
Laura A. Forney ◽  
Thomas W. Gettys
Keyword(s):  
Amino Acids ◽  
Dietary Protein ◽  
Target Genes ◽  
Protein Restriction ◽  
Metabolic Phenotype ◽  
Sulfur Amino Acids ◽  
Transcriptional Responses ◽  
Similar Reduction ◽  
Dietary Protein Restriction ◽  
Methionine Restriction

Dietary protein restriction and dietary methionine restriction (MR) produce a comparable series of behavioral, physiological, biochemical, and transcriptional responses. Both dietary regimens produce a similar reduction in intake of sulfur amino acids (e.g., methionine and cystine), and both diets increase expression and release of hepatic FGF21. Given that FGF21 is an essential mediator of the metabolic phenotype produced by both diets, an important unresolved question is whether dietary protein restriction represents de facto methionine restriction. Using diets formulated from either casein or soy protein with matched reductions in sulfur amino acids, we compared the ability of the respective diets to recapitulate the metabolic phenotype produced by methionine restriction using elemental diets. Although the soy-based control diets supported faster growth compared to casein-based control diets, casein-based protein restriction and soy-based protein restriction produced comparable reductions in body weight and fat deposition, and similar increases in energy intake, energy expenditure, and water intake. In addition, the prototypical effects of dietary MR on hepatic and adipose tissue target genes were similarly regulated by casein- and soy-based protein restriction. The present findings support the feasibility of using restricted intake of diets from various protein sources to produce therapeutically effective implementation of dietary methionine restriction.

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