mmBCFA C17iso ensures endoplasmic reticulum integrity for lipid droplet growth

2021 ◽  
Vol 220 (11) ◽  
Author(s):  
Jingjing Zhang ◽  
Ying Hu ◽  
Yanli Wang ◽  
Lin Fu ◽  
Xiumei Xu ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Membrane Integrity ◽  
Lipid Synthesis ◽  
Droplet Growth ◽  
Side Chain ◽  
C Elegans ◽  
Branched Chain Fatty Acids ◽  
Intracellular Organelles ◽  
Branched Chain ◽  
Er Homeostasis

In eukaryote cells, lipid droplets (LDs) are key intracellular organelles that dynamically regulate cellular energy homeostasis. LDs originate from the ER and continuously contact the ER during their growth. How the ER affects LD growth is largely unknown. Here, we show that RNAi knockdown of acs-1, encoding an acyl-CoA synthetase required for the biosynthesis of monomethyl branched-chain fatty acids C15iso and C17iso, remarkably prevented LD growth in Caenorhabditis elegans. Dietary C17iso, or complex lipids with C17iso including phosphatidylcholine, phosphatidylethanolamine, and triacylglycerol, could fully restore the LD growth in the acs-1RNAi worms. Mechanistically, C17iso may incorporate into phospholipids to ensure the membrane integrity of the ER so as to maintain the function of ER-resident enzymes such as SCD/stearoyl-CoA desaturase and DGAT2/diacylglycerol acyltransferase for appropriate lipid synthesis and LD growth. Collectively, our work uncovers a unique fatty acid, C17iso, as the side chain of phospholipids for determining the ER homeostasis for LD growth in an intact organism, C. elegans.

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 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 The Stool Volatile Metabolome of Pre-Term Babies

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3341
Author(s):  
Alessandra Frau ◽  
Lauren Lett ◽  
Rachael Slater ◽  
Gregory R. Young ◽  
Christopher J. Stewart ◽  
...  
Keyword(s):  
Early Life ◽  
Solid Phase ◽  
Mass Spectrometry Data ◽  
Gas Chromatography Mass Spectrometry ◽  
Mass Spectral ◽  
Branched Chain Fatty Acids ◽  
Volatile Organic ◽  
Stool Samples ◽  
Branched Chain ◽  
Mixed Modelling

The fecal metabolome in early life has seldom been studied. We investigated its evolution in pre-term babies during their first weeks of life. Multiple (n = 152) stool samples were studied from 51 babies, all <32 weeks gestation. Volatile organic compounds (VOCs) were analyzed by headspace solid phase microextraction gas chromatography mass spectrometry. Data were interpreted using Automated Mass Spectral Deconvolution System (AMDIS) with the National Institute of Standards and Technology (NIST) reference library. Statistical analysis was based on linear mixed modelling, the number of VOCs increased over time; a rise was mainly observed between day 5 and day 10. The shift at day 5 was associated with products of branched-chain fatty acids. Prior to this, the metabolome was dominated by aldehydes and acetic acid. Caesarean delivery showed a modest association with molecules of fungal origin. This study shows how the metabolome changes in early life in pre-term babies. The shift in the metabolome 5 days after delivery coincides with the establishment of enteral feeding and the transition from meconium to feces. Great diversity of metabolites was associated with being fed greater volumes of milk.

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.

scholarly journals Chicken-eaters and pork-eaters have different gut microbiota and tryptophan metabolites

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jie Shi ◽  
Di Zhao ◽  
Fan Zhao ◽  
Chong Wang ◽  
Galia Zamaratskaia ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Gut Microbiota ◽  
Short Chain Fatty Acids ◽  
Short Chain ◽  
Branched Chain Fatty Acids ◽  
Tryptophan Metabolites ◽  
Branched Chain ◽  
Spearman’S Correlation ◽  
Gut Microbiota Composition ◽  
Chain Fatty Acids

AbstractThis study was aimed to evaluate the differences in the composition of gut microbiota, tryptophan metabolites and short-chain fatty acids in feces between volunteers who frequently ate chicken and who frequently ate pork. Twenty male chicken-eaters and 20 male pork-eaters of 18 and 30 years old were recruited to collect feces samples for analyses of gut microbiota composition, short-chain fatty acids and tryptophan metabolites. Chicken-eaters had more diverse gut microbiota and higher abundance of Prevotella 9, Dialister, Faecalibacterium, Megamonas, and Prevotella 2. However, pork-eaters had higher relative abundance of Bacteroides, Faecalibacterium, Roseburia, Dialister, and Ruminococcus 2. In addition, chicken-eaters had high contents of skatole and indole in feces than pork-eaters, as well as higher contents of total short chain fatty acids, in particular for acetic acid, propionic acid, and branched chain fatty acids. The Spearman’s correlation analysis revealed that the abundance of Prevotella 2 and Prevotella 9 was positively correlated with levels of fecal skatole, indole and short-chain fatty acids. Thus, intake of chicken diet may increase the risk of skatole- and indole-induced diseases by altering gut microbiota.

Sign in / Sign up

Export Citation Format

Share Document