scholarly journals Natural variation inC. elegansarsenic toxicity is explained by differences in branched chain amino acid metabolism

2018 ◽  
Author(s):  
Stefan Zdraljevic ◽  
Bennett W. Fox ◽  
Christine Strand ◽  
Oishika Panda ◽  
Francisco J. Tenjo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Amino Acid ◽  
Human Populations ◽  
C Elegans ◽  
Branched Chain Amino Acid ◽  
Branched Chain Fatty Acids ◽  
Synonymous Variant ◽  
Branched Chain ◽  
Lipoyl Domain ◽  
Chain Fatty Acids

AbstractWe find that variation in thedbt-1gene underlies natural differences inCaenorhabditis elegansresponses to the toxin arsenic. This gene encodes the E2 subunit of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, a core component of branched-chain amino acid (BCAA) metabolism. We causally linked a non-synonymous variant in the conserved lipoyl domain of DBT-1 to differential arsenic responses. Using targeted metabolomics and chemical supplementation, we demonstrate that differences in responses to arsenic are caused by variation in iso-branched chain fatty acids. Additionally, we show that levels of branched chain fatty acids in human cells are perturbed by arsenic treatment. This finding has broad implications for arsenic toxicity and for arsenic-focused chemotherapeutics across human populations. Our study implicates the BCKDH complex and BCAA metabolism in arsenic responses, demonstrating the power ofC. elegansnatural genetic diversity to identify novel mechanisms by which environmental toxins affect organismal physiology.

scholarly journals Natural variation in C. elegans arsenic toxicity is explained by differences in branched chain amino acid metabolism

eLife ◽  
2019 ◽  
Vol 8 ◽  
Author(s):  
Stefan Zdraljevic ◽  
Bennett William Fox ◽  
Christine Strand ◽  
Oishika Panda ◽  
Francisco J Tenjo ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Amino Acid ◽  
Editorial Note ◽  
Human Populations ◽  
Arsenic Toxicity ◽  
C Elegans ◽  
Branched Chain Amino Acid ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Chain Fatty Acids

We find that variation in the dbt-1 gene underlies natural differences in Caenorhabditis elegans responses to the toxin arsenic. This gene encodes the E2 subunit of the branched-chain α-keto acid dehydrogenase (BCKDH) complex, a core component of branched-chain amino acid (BCAA) metabolism. We causally linked a non-synonymous variant in the conserved lipoyl domain of DBT-1 to differential arsenic responses. Using targeted metabolomics and chemical supplementation, we demonstrate that differences in responses to arsenic are caused by variation in iso-branched chain fatty acids. Additionally, we show that levels of branched chain fatty acids in human cells are perturbed by arsenic treatment. This finding has broad implications for arsenic toxicity and for arsenic-focused chemotherapeutics across human populations. Our study implicates the BCKDH complex and BCAA metabolism in arsenic responses, demonstrating the power of C. elegans natural genetic diversity to identify novel mechanisms by which environmental toxins affect organismal physiology.Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (<xref ref-type="decision-letter" rid="SA1">see decision letter</xref>).

scholarly journals Stool pH and Short/Branched Chain Fatty Acids in Infants Receiving Extensively Hydrolyzed Formula, Amino Acid Formula, or Human Milk Through Two Months of Age (P11-076-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Car Reen Kok ◽  
Bradford Brabec ◽  
Maciej Chichlowski ◽  
Cheryl Harris ◽  
Nancy Moore ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Amino Acid ◽  
Human Milk ◽  
Dietary Protein ◽  
Fused Silica ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Mother’S Own Milk ◽  
Different Sources ◽  
Chain Fatty Acids

Abstract Objectives Infant feeding influences early development of the gut microbiome, colonization pattern, and community structure. Metabolites, including short- and branched-chain fatty acids (S/BCFA) (e.g., butyrate, propionate), produced by colonic bacteria serve as signaling molecules, influence immunity, and reduce luminal pH in the gastrointestinal environment. The objective of this study was to evaluate stool S/BCFA and pH in infants fed with different sources of dietary protein. Methods In this multicenter, double-blind, controlled, parallel-group, pilot study, healthy term infants were randomized to receive one of two infant formulas (IF): amino-acid based (AAF; n = 25) or extensively hydrolyzed cow's milk protein (EHF; n = 28) from Baseline (1-7 days of age) up to 60 days of age. A human milk reference group (HM; n = 25) received mother's own milk over the same period. Diethyl ether extractions of S/BCFA from stool samples (Baseline, Day 30, and Day 60) were quantified by gas chromatography (Clarus 580; PerkinElmer) using a fused silica capillary column (Nukol 30m × 0.25mm id × 0.25μm film). Mean stool S/BCFA (μmol/g) and pH were analyzed by repeated measures analysis of variance (ANOVA). Results Complete stool data (all study time points) were available for 49 participants. Stool pH (∼6) was similar among groups at Baseline with no significant changes for HM and EHF groups through Day 60. The AAF group was significantly higher at Days 30 and 60 (Figure 1). Total SCFA were similar for all groups through Day 60. Butyrate increased significantly from Baseline to Day 60 in the EHF group (P = 0.026) and was significantly higher vs HM at Days 30 and 60 (P = 0.0009 and 0.0004 respectively). Butyrate was significantly higher for AAF vs HM at Day 60 only (P = 0.038). Propionate was significantly higher for EHF and AAF at Day 30 (P = 0.0009 and < 0.0001 respectively) and AAF only at Day 60 (P = 0.005) vs HM. Total and individual BCFA increased for AAF and EHF groups vs HM through Day 60. Conclusions Distinct patterns of pH and microbial metabolites were demonstrated for infants receiving mother's own milk compared to amino acid-based or extensively hydrolyzed protein formula. Providing different sources of dietary protein early in life may influence gut microbiota and metabolites. Funding Sources Mead Johnson Pediatric Nutrition Institute. Supporting Tables, Images and/or Graphs

scholarly journals Monomethyl branched-chain fatty acids are critical for C. elegans survival in elevated glucose conditions

2021 ◽  
pp. 101444
Author(s):  
Andre F.C. Vieira ◽  
Mark A. Xatse ◽  
Hamide Tifeki ◽  
Cédric Diot ◽  
Albertha J.M. Walhout ◽  
...  
Keyword(s):  
Fatty Acids ◽  
C Elegans ◽  
Branched Chain Fatty Acids ◽  
Elevated Glucose ◽  
Branched Chain ◽  
Chain Fatty Acids

scholarly journals Role of Aminotransferase IlvE in Production of Branched-Chain Fatty Acids by Lactococcus lactis subsp. lactis

2004 ◽  
Vol 70 (1) ◽  
pp. 638-641 ◽  
Author(s):  
Balasubramanian Ganesan ◽  
Bart C. Weimer
Keyword(s):  
Fatty Acids ◽  
Lactococcus Lactis ◽  
Deletion Mutant ◽  
Keto Acid ◽  
Branched Chain Amino Acid ◽  
Branched Chain Fatty Acids ◽  
Keto Acids ◽  
Branched Chain ◽  
Chain Fatty Acids

ABSTRACT The objective of this study was to determine the role of a lactococcal branched-chain amino acid aminotransferase gene, ilvE, in the production of branched-chain fatty acids. Lactococcus lactis subsp. lactis LM0230 and an ilvE deletion mutant, JLS450, produced branched-chain fatty acids from amino and α-keto acids at levels above α-keto acid spontaneous degradation and the fatty acids' flavor thresholds. The deletion mutant produced the same amounts of branched-chain fatty acids from precursor amino acids as did the parent. This was not the case, however, for the production of branched-chain fatty acids from the corresponding precursor α-keto acids. The deletion mutant produced a set of fatty acids different from that produced by the parent. We concluded from these observations that ilvE plays a role in the specific type of fatty acids produced but has little influence on the total amount of fatty acids produced by lactococci.

scholarly journals Short- and Branched-Chain Fatty Acids as Fecal Markers for Microbiota Activity in Vegans and Omnivores

Nutrients ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1808
Author(s):  
Iris Trefflich ◽  
Stefan Dietrich ◽  
Annett Braune ◽  
Klaus Abraham ◽  
Cornelia Weikert
Keyword(s):  
Fatty Acids ◽  
Ammonia Concentration ◽  
Cross Sectional Study ◽  
Vegan Diet ◽  
Microbiota Composition ◽  
Cross Sectional ◽  
Branched Chain Fatty Acids ◽  
Branched Chain ◽  
Fecal Ph ◽  
Chain Fatty Acids

A vegan diet could impact microbiota composition and bacterial metabolites like short-chain (SCFA) and branched-chain fatty acids (BCFA). The aim of this study was to compare the concentrations of SCFA, BCFA, ammonia, and fecal pH between vegans and omnivores. In this cross-sectional study (vegans n = 36; omnivores n = 36), microbiota composition, fecal SCFA, BCFA, and ammonia concentrations and pH were analyzed in complete stool samples. A random forest regression (RFR) was used to identify bacteria predicting SCFA/BCFA concentrations in vegans and omnivores. No significant differences in SCFA and BCFA concentrations were observed between vegans and omnivores. Fecal pH (p = 0.005) and ammonia concentration (p = 0.01) were significantly lower in vegans than in omnivores, while fiber intake was higher (p < 0.0001). Shannon diversity was higher in omnivores compared to vegans on species level (p = 0.04) only. In vegans, a cluster of Faecalibacterium prausnitzii, Prevotella copri, Dialister spp., and Eubacterium spp. was predictive for SCFA and BCFA concentrations. In omnivores, Bacteroides spp., Clostridium spp., Ruminococcus spp., and Prevotella copri were predictive. Though SCFA and BCFA did not differ between vegans and omnivores, the results of the RFR suggest that bacterial functionality may be adapted to varying nutrient availability in these diets.

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