scholarly journals Mice Lacking the Intestinal and Renal Neutral Amino Acid Transporter SLC6A19 Demonstrate the Relationship between Dietary Protein Intake and Amino Acid Malabsorption

Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2024 ◽  
Author(s):  
Kiran Javed ◽  
Stefan Bröer

Dietary protein restriction has beneficial impacts on metabolic health. B0AT1 (SLC6A19) is the major transporter of neutral amino acids at the intestinal epithelia and absorbs the bulk of the diet-derived neutral amino acids from the intestinal lumen. It also reabsorbs neutral amino acids in the renal proximal tubules. Mice lacking B0AT1 show cellular outcomes of protein restriction, such as high FGF21 levels and low mTORC1 activity. Moreover, they have improved glucose homeostasis and resist diet-induced obesity. In this study, we investigated the relationship between protein restriction and dietary protein intake in C57Bl6/J wild-type (wt) and SLC6A19-knockout (SLC6A19ko) mice. When SLC6A19ko mice were fed diets containing 5%, 25%, or 52% of their total calories derived from protein, no differences in food intake or weight gain were observed. All essential amino acids significantly positively correlated with increasing dietary casein content in the wt mice. The SLC6A19ko mice showed reduced postprandial levels of essential amino acids in plasma, particularly following high-protein diets. Upon fasting, essential amino acids were the same in the wt and SLC6A19ko mice due to reduced amino acid catabolism. Bacterial metabolites originating from amino acid fermentation correlated with the dietary protein content, but showed a complex profile in the blood of the SLC6A19ko mice. This study highlights the potential of SLC6A19 as a knock-out or inhibition target to induce protein restriction for the treatment of metabolic disorders.

2016 ◽  
Vol 53 (4) ◽  
pp. 380
Author(s):  
Sarita Devi ◽  
Tinku Thomas ◽  
Pratibha Dwarkanath ◽  
Annamma Thomas ◽  
C. N. Sheela ◽  
...  

Low intakes of quality dietary protein could affect the methionine cycle during pregnancy, which is important for fetal growth and epigenetic regulations. Since low quality protein intake is prevalent in India, it is important to define biomarkers of the low protein intake, specifically of methyl cycle homeostasis. A secondary analysis of data was performed, from a randomized intervention trial with 500 ml milk/d on south Indian pregnant women, to examine the association of dietary protein intake with concentrations of specific amino acids (methionine, glycine and serine). The subjects also underwent isotopic infusions (n = 52) for the measurement of amino acid kinetics. Dietary intakes were measured each week by multiple 24 h recall until delivery. The plasma concentrations of amino acids (methionine, serine and glycine) were compared with kinetics of methionine i.e. transmethylation, remethylation and transulfuration (TM, RM, TS) and serine to glycine conversion rates, as measured by stable isotope labeled amino acid infusion. Dietary protein intake in the 3<sup>rd</sup> trimester correlated positively with intakes of milk and milk based food products (ρ=0.52, p&lt;0.001) and methionine (ρ=0.97, p&lt;0.001) and with gestational weight gain (GWG, ρ=0.32, p=0.044). While the methionine concentration did not correlate with methyl cycle flux parameters (TM, RM and TS), the plasma concentrations of conditionally essential serine and glycine were positively correlated with their respective flux rate and with RM, TM and TS rates. Further, glycine concentrations specifically correlated positively with serine to glycine conversion rates (ρ=0.32, p=0.027). Dietary protein and methionine supply are important for the conservation of methionine during pregnancy. This had an effect on GWG, but not on birth weight, though this may have been due to the relatively small sample size. The plasma concentration of glycine was correlated with the serine-glycine conversion, which affords methyl groups for the body and supplies these when dietary protein/methionine is in poor supply. This indicates that itcan act as a biomarker of the serine-glycine conversion flux rate, which increases in the presence of a poor protein supply. In general, the plasma concentrations of these conditionally essential amino acids may be biomarkers of the methyl cycle during pregnancy, but this needs to be tested in a larger sample.


2018 ◽  
Vol 243 (6) ◽  
pp. 525-533 ◽  
Author(s):  
Cassandra M Herring ◽  
Fuller W Bazer ◽  
Gregory A Johnson ◽  
Guoyao Wu

Maternal nutrition during gestation, especially dietary protein intake, is a key determinant in embryonic survival, growth, and development. Low maternal dietary protein intake can cause embryonic losses, intra-uterine growth restriction, and reduced postnatal growth due to a deficiency in specific amino acids that are important for cell metabolism and function. Of note, high maternal dietary protein intake can also result in intra-uterine growth restriction and embryonic death, due to amino acid excesses, as well as the toxicity of ammonia, homocysteine, and H2S that are generated from amino acid catabolism. Maternal protein nutrition has a pronounced impact on fetal programming and alters the expression of genes in the fetal genome. As a precursor to the synthesis of molecules (e.g. nitric oxide, polyamines, and creatine) with cell signaling and metabolic functions, L-arginine (Arg) is essential during pregnancy for growth and development of the conceptus. With inadequate maternal dietary protein intake, Arg and other important amino acids are deficient in mother and fetus. Dietary supplementation of Arg during gestation has been effective in improving embryonic survival and development of the conceptus in many species, including humans, pigs, sheep, mice, and rats. Both the balance among amino acids and their quantity are critical for healthy pregnancies and offspring. Impact statement This review aims at: highlighting adverse effects of elevated levels of ammonia in mother or fetus on embryonic/fetal survival, growth, and development; helping nutritionists and practitioners to understand the mechanisms whereby elevated levels of ammonia in mother or fetus results in embryonic/fetal death, growth restriction, and developmental abnormalities; and bringing, into the attention of nutritionists and practitioners, the problems of excess or inadequate dietary intake of protein or amino acids on pregnancy outcomes in animals and humans. The article provides new, effective means to improve embryonic/fetal survival and growth in mammals.


2008 ◽  
Vol 22 (11) ◽  
pp. 745-754 ◽  
Author(s):  
Y F Wang ◽  
WS Yancy Jr ◽  
D Yu ◽  
C Champagne ◽  
L J Appel ◽  
...  

1981 ◽  
Vol 240 (6) ◽  
pp. E712-E721 ◽  
Author(s):  
K. J. Motil ◽  
D. E. Matthews ◽  
D. M. Bier ◽  
J. F. Burke ◽  
H. N. Munro ◽  
...  

Whole-body leucine and lysine metabolism was explored in young adult men by a primed constant intravenous infusion of a mixture of L-[1–13C]leucine and L-[alpha-15N]lysine over a 4-h period. Subjects were studied after an overnight fast (postabsorptive state) or while consuming hourly meals (fed state) after adaptation to diets providing either a surfeit level of protein (1.5 g.kg body-1.day-1), a level approximating maintenance requirements (marginal intake) (0.6 g.kg body wt-1.day-1), or a grossly inadequate level (0.1 g.kg-1.day-1). The change in protein intake from a marginal to a surfeit level was associated with an increased leucine flux and incorporation of leucine into body protein. In the fed state, oxidation of leucine increased sharply and release of leucine from tissue protein diminished. When dietary protein intake was reduced from the requirement to inadequate level, leucine flux and body protein synthesis and protein breakdown were reduced, together with a smaller reduction in leucine oxidation. The response of the metabolism of [15N]lysine was responsible for maintenance of leucine and other essential amino acid economy, and they appear to be related to the nitrogen and amino acid requirements of the subject. These findings also demonstrate an effect of meals, modulated by their protein content, on the dynamics of whole-body amino acid metabolism.


Nutrients ◽  
2019 ◽  
Vol 11 (9) ◽  
pp. 2190 ◽  
Author(s):  
Allman ◽  
Diaz Fuentes ◽  
Williams ◽  
Turner ◽  
Andres ◽  
...  

The purpose of this study was to determine the associations between amount and type of dietary protein intake and insulin sensitivity in late pregnancy, in normal weight and overweight women (29.8 ± 0.2 weeks gestation, n = 173). A 100-gram oral glucose tolerance test (OGTT) was administered following an overnight fast to estimate the metabolic clearance rate of glucose (MCR, mg · kg-1 · min-1) using four different equations accounting for the availability of blood samples. Total (TP), animal (AP), and plant (PP) protein intakes were assessed using a 3-day food record. Two linear models with MCR as the response variable were fitted to the data to estimate the relationship of protein intake to insulin sensitivity either unadjusted or adjusted for early pregnancy body mass index (BMI) because of the potential of BMI to influence this relationship. There was a positive association between TP (β = 1.37, p = 0.002) and PP (β = 4.44, p < 0.001) intake in the last trimester of pregnancy and insulin sensitivity that weakened when accounting for early pregnancy BMI. However, there was no relationship between AP intake and insulin sensitivity (β = 0.95, p = 0.08). Therefore, early pregnancy BMI may be a better predictor of insulin sensitivity than dietary protein intake in late pregnancy.


2019 ◽  
Vol 109 (3) ◽  
pp. 517-525 ◽  
Author(s):  
Casey M Rebholz ◽  
Zihe Zheng ◽  
Morgan E Grams ◽  
Lawrence J Appel ◽  
Mark J Sarnak ◽  
...  

ABSTRACT Background Accurate assessment of dietary intake is essential, but self-report of dietary intake is prone to measurement error and bias. Discovering metabolic consequences of diets with lower compared with higher protein intake could elucidate new, objective biomarkers of protein intake. Objectives The goal of this study was to identify serum metabolites associated with dietary protein intake. Methods Metabolites were measured with the use of untargeted, reverse-phase ultra-performance liquid chromatography–tandem mass spectrometry quantification in serum specimens collected at the 12-mo follow-up visit in the Modification of Diet in Renal Disease (MDRD) Study from 482 participants in study A (glomerular filtration rate: 25–55 mL · min−1 · 1.73 m−2) and 192 participants in study B (glomerular filtration rate: 13–24 mL · min−1 · 1.73 m−2). We used multivariable linear regression to test for differences in log-transformed metabolites (outcome) according to randomly assigned dietary protein intervention groups (exposure). Statistical significance was assessed at the Bonferroni-corrected threshold: 0.05/1193 = 4.2 × 10−5. Results In study A, 130 metabolites (83 known from 28 distinct pathways, including 7 amino acid pathways; 47 unknown) were significantly different between participants randomly assigned to the low-protein diet compared with the moderate-protein diet. In study B, 32 metabolites (22 known from 8 distinct pathways, including 4 amino acid pathways; 10 unknown) were significantly different between participants randomly assigned to the very-low-protein diet compared with the low-protein diet. A total of 11 known metabolites were significantly associated with protein intake in the same direction in both studies A and B: 3-methylhistidine, N-acetyl-3-methylhistidine, xanthurenate, isovalerylcarnitine, creatine, kynurenate, 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPE (P-16:0/20:4), 1-(1-enyl-stearoyl)-2-arachidonoyl-GPE (P-18:0/20:4), 1-(1-enyl-palmitoyl)-2-arachidonoyl-GPC (P-16:0/20:4), sulfate, and γ-glutamylalanine. Conclusions Among patients with chronic kidney disease, an untargeted serum metabolomics platform identified multiple pathways and metabolites associated with dietary protein intake. Further research is necessary to characterize unknown compounds and to examine these metabolites in association with dietary protein intake among individuals without kidney disease. This trial was registered at clinicaltrials.gov as NCT03202914.


Bone ◽  
2010 ◽  
Vol 47 ◽  
pp. S211
Author(s):  
C.S. McDonald ◽  
G.C. Chan ◽  
N.P. Kennedy ◽  
Z. Toth ◽  
J.B. Walsh ◽  
...  

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