scholarly journals Effect of dietary protein restriction on renal ammonia metabolism

2015 ◽  
Vol 308 (12) ◽  
pp. F1463-F1473 ◽  
Author(s):  
Hyun-Wook Lee ◽  
Gunars Osis ◽  
Mary E. Handlogten ◽  
Hui Guo ◽  
Jill W. Verlander ◽  
...  
Keyword(s):  
Dietary Protein ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Primary Component ◽  
Protein Restriction ◽  
Acid Excretion ◽  
Ammonia Metabolism ◽  
Dietary Protein Restriction ◽  
Ammonia Transport ◽  
Net Acid Excretion

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 change in parallel during protein restriction. Ammonia is the primary component of net acid excretion, and inappropriate ammonia excretion can lead to negative nitrogen balance. Accordingly, we examined ammonia excretion in response to protein restriction and then we determined the molecular mechanism of the changes observed. Wild-type C57Bl/6 mice fed a 20% protein diet and then changed to 6% protein developed an 85% reduction in ammonia excretion within 2 days, which persisted during a 10-day study. The expression of multiple proteins involved in renal ammonia metabolism was altered, including the ammonia-generating enzymes phosphate-dependent glutaminase (PDG) and phospho enolpyruvate carboxykinase (PEPCK) and the ammonia-metabolizing enzyme glutamine synthetase. Rhbg, an ammonia transporter, increased in expression in the inner stripe of outer medullary collecting duct intercalated cell (OMCDis-IC). However, collecting duct-specific Rhbg deletion did not alter the response to protein restriction. Rhcg deletion did not alter ammonia excretion in response to dietary protein restriction. These results indicate 1) dietary protein restriction decreases renal ammonia excretion through coordinated regulation of multiple components of ammonia metabolism; 2) increased Rhbg expression in the OMCDis-IC may indicate a biological role in addition to ammonia transport; and 3) Rhcg expression is not necessary to decrease ammonia excretion during dietary protein restriction.

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.

scholarly journals Ammonia Transporters and Their Role in Acid-Base Balance

2017 ◽  
Vol 97 (2) ◽  
pp. 465-494 ◽  
Author(s):  
I. David Weiner ◽  
Jill W. Verlander
Keyword(s):  
Ammonia Excretion ◽  
Transport Processes ◽  
Molecular Forms ◽  
Acid Excretion ◽  
Acid Base ◽  
Titratable Acid ◽  
Renal Net Acid Excretion ◽  
Ammonia Transport ◽  
Specific Proteins ◽  
Net Acid Excretion

Acid-base homeostasis is critical to maintenance of normal health. Renal ammonia excretion is the quantitatively predominant component of renal net acid excretion, both under basal conditions and in response to acid-base disturbances. Although titratable acid excretion also contributes to renal net acid excretion, the quantitative contribution of titratable acid excretion is less than that of ammonia under basal conditions and is only a minor component of the adaptive response to acid-base disturbances. In contrast to other urinary solutes, ammonia is produced in the kidney and then is selectively transported either into the urine or the renal vein. The proportion of ammonia that the kidney produces that is excreted in the urine varies dramatically in response to physiological stimuli, and only urinary ammonia excretion contributes to acid-base homeostasis. As a result, selective and regulated renal ammonia transport by renal epithelial cells is central to acid-base homeostasis. Both molecular forms of ammonia, NH3 and NH4+, are transported by specific proteins, and regulation of these transport processes determines the eventual fate of the ammonia produced. In this review, we discuss these issues, and then discuss in detail the specific proteins involved in renal epithelial cell ammonia transport.

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.

scholarly journals Differences in acidosis-stimulated renal ammonia metabolism in the male and female kidney

2019 ◽  
Vol 317 (4) ◽  
pp. F890-F905 ◽  
Author(s):  
Autumn N. Harris ◽  
Hyun-Wook Lee ◽  
Lijuan Fang ◽  
Jill W. Verlander ◽  
I. David Weiner
Keyword(s):  
Phosphoenolpyruvate Carboxykinase ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Volume Density ◽  
Male Mice ◽  
Ammonia Metabolism ◽  
Female Mice ◽  
Predominant Component ◽  
Acid Load ◽  
Acid Loading

Renal ammonia excretion is a critical component of acid-base homeostasis, and changes in ammonia excretion are the predominant component of increased net acid excretion in response to metabolic acidosis. We recently reported substantial sex-dependent differences in basal ammonia metabolism that correlate with sex-dependent differences in renal structure and expression of key proteins involved in ammonia metabolism. The purpose of the present study was to investigate the effect of sex on the renal ammonia response to an exogenous acid load. We studied 4-mo-old C57BL/6 mice. Ammonia excretion, which was less in male mice under basal conditions, increased in response to acid loading to a greater extent in male mice, such that maximal ammonia excretion did not differ between the sexes. Fundamental structural sex differences in the nonacid-loaded kidney persisted after acid loading, with less cortical proximal tubule volume density in the female kidney than in the male kidney, whereas collecting duct volume density was greater in the female kidney. To further investigate sex-dependent differences in the response to acid loading, we examined the expression of proteins involved in ammonia metabolism. The change in expression of phosphoenolpyruvate carboxykinase and Rh family B glycoprotein with acid loading was greater in male mice than in female mice, whereas Na+-K+-2Cl– cotransporter and inner stripe of the outer medulla intercalated cell Rh family C glycoprotein expression were significantly greater in female mice than in male mice. There was no significant sex difference in glutamine synthetase, Na+/H+ exchanger isoform 3, or electrogenic Na+-bicarbonate cotransporter 1 variant A protein expression in response to acid loading. We conclude that substantial sex-dependent differences in the renal ammonia response to acid loading enable a similar maximum ammonia excretion response.

scholarly journals More actors in ammonia absorption by the thick ascending limb

2012 ◽  
Vol 302 (3) ◽  
pp. F293-F297 ◽  
Author(s):  
Pascal Houillier ◽  
Soline Bourgeois
Keyword(s):  
Current Knowledge ◽  
Collecting Duct ◽  
Ammonia Excretion ◽  
Hydrogen Ion ◽  
Thick Ascending Limb ◽  
Loop Of Henle ◽  
Transport Mechanisms ◽  
Sodium Hydrogen ◽  
Ammonia Transport ◽  
Ammonia Absorption

This review will briefly summarize current knowledge on the basolateral ammonia transport mechanisms in the thick ascending limb (TAL) of the loop of Henle. This segment transports ammonia against a concentration gradient and is responsible for the accumulation of ammonia in the medullary interstitium, which, in turn, favors ammonia secretion across the collecting duct. Experimental data indicate that the sodium/hydrogen ion exchanger isoform 4 (NHE4; Scl9a4) is a sodium/ammonia exchanger and plays a major role in this process. Disruption of murine NHE4 leads to metabolic acidosis with inappropriate urinary ammonia excretion and decreases the ability of the TAL to absorb ammonia and to build the corticopapillary ammonia gradient. However, NHE4 does not account for the entirety of ammonia absorption by the TAL, indicating that, at least, one more transporter is involved.

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