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  1. Article ; Online: Peripheral peroxisomal β-oxidation engages neuronal serotonin signaling to drive stress-induced aversive memory in C. elegans.

    Tsai, Shang-Heng / Wu, Yu-Chun / Palomino, Diana Fajardo / Schroeder, Frank C / Pan, Chun-Liang

    Cell reports

    2024  Volume 43, Issue 4, Page(s) 113996

    Abstract: Physiological dysfunction confers negative valence to coincidental sensory cues to induce the formation of aversive associative memory. How peripheral tissue stress engages neuromodulatory mechanisms to form aversive memory is poorly understood. Here, we ...

    Abstract Physiological dysfunction confers negative valence to coincidental sensory cues to induce the formation of aversive associative memory. How peripheral tissue stress engages neuromodulatory mechanisms to form aversive memory is poorly understood. Here, we show that in the nematode C. elegans, mitochondrial disruption induces aversive memory through peroxisomal β-oxidation genes in non-neural tissues, including pmp-4/very-long-chain fatty acid transporter, dhs-28/3-hydroxylacyl-CoA dehydrogenase, and daf-22/3-ketoacyl-CoA thiolase. Upregulation of peroxisomal β-oxidation genes under mitochondrial stress requires the nuclear hormone receptor NHR-49. Importantly, the memory-promoting function of peroxisomal β-oxidation is independent of its canonical role in pheromone production. Peripheral signals derived from the peroxisomes target NSM, a critical neuron for memory formation under stress, to upregulate serotonin synthesis and remodel evoked responses to sensory cues. Our genetic, transcriptomic, and metabolomic approaches establish peroxisomal lipid signaling as a crucial mechanism that connects peripheral mitochondrial stress to central serotonin neuromodulation in aversive memory formation.
    MeSH term(s) Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans/physiology ; Peroxisomes/metabolism ; Serotonin/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Caenorhabditis elegans Proteins/genetics ; Signal Transduction ; Oxidation-Reduction ; Memory/physiology ; Mitochondria/metabolism ; Neurons/metabolism ; Stress, Physiological ; Receptors, Cytoplasmic and Nuclear/metabolism
    Chemical Substances Serotonin (333DO1RDJY) ; Caenorhabditis elegans Proteins ; NHR-49 protein, C elegans ; Receptors, Cytoplasmic and Nuclear
    Language English
    Publishing date 2024-03-24
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2024.113996
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans.

    Fox, Bennett W / Helf, Maximilian J / Burkhardt, Russell N / Artyukhin, Alexander B / Curtis, Brian J / Palomino, Diana Fajardo / Schroeder, Allen F / Chaturbedi, Amaresh / Tauffenberger, Arnaud / Wrobel, Chester J J / Zhang, Ying K / Lee, Siu Sylvia / Schroeder, Frank C

    Nature communications

    2024  Volume 15, Issue 1, Page(s) 1520

    Abstract: Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the ... ...

    Abstract Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression, but the underlying mechanisms have remained unclear. Here, we show that endogenous and microbiota-dependent small molecule signals promote lipid desaturation via the nuclear receptor NHR-49/PPARα in C. elegans. Untargeted metabolomics of a β-oxidation mutant, acdh-11, in which expression of the stearoyl-CoA desaturase FAT-7/SCD1 is constitutively increased, revealed accumulation of a β-cyclopropyl fatty acid, becyp#1, that potently activates fat-7 expression via NHR-49. Biosynthesis of becyp#1 is strictly dependent on expression of cyclopropane synthase by associated bacteria, e.g., E. coli. Screening for structurally related endogenous metabolites revealed a β-methyl fatty acid, bemeth#1, which mimics the activity of microbiota-dependent becyp#1 but is derived from a methyltransferase, fcmt-1, that is conserved across Nematoda and likely originates from bacterial cyclopropane synthase via ancient horizontal gene transfer. Activation of fat-7 expression by these structurally similar metabolites is controlled by distinct mechanisms, as microbiota-dependent becyp#1 is metabolized by a dedicated β-oxidation pathway, while the endogenous bemeth#1 is metabolized via α-oxidation. Collectively, we demonstrate that evolutionarily related biosynthetic pathways in metazoan host and associated microbiota converge on NHR-49/PPARα to regulate fat desaturation.
    MeSH term(s) Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; PPAR alpha/metabolism ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Fatty Acids/metabolism ; Cyclopropanes/metabolism
    Chemical Substances Caenorhabditis elegans Proteins ; PPAR alpha ; Fatty Acids ; Cyclopropanes
    Language English
    Publishing date 2024-02-19
    Publishing country England
    Document type Journal Article
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-024-45782-2
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Natural genetic variation in the pheromone production of

    Lee, Daehan / Fox, Bennett W / Palomino, Diana Fajardo / Panda, Oishika / Tenjo, Francisco J / Koury, Emily J / Evans, Kathryn S / Stevens, Lewis / Rodrigues, Pedro R / Kolodziej, Aiden R / Schroeder, Frank C / Andersen, Erik C

    Proceedings of the National Academy of Sciences of the United States of America

    2023  Volume 120, Issue 26, Page(s) e2221150120

    Abstract: From bacterial quorum sensing to human language, communication is essential for social interactions. Nematodes produce and sense pheromones to communicate among individuals and respond to environmental changes. These signals are encoded by different ... ...

    Abstract From bacterial quorum sensing to human language, communication is essential for social interactions. Nematodes produce and sense pheromones to communicate among individuals and respond to environmental changes. These signals are encoded by different types and mixtures of ascarosides, whose modular structures further enhance the diversity of this nematode pheromone language. Interspecific and intraspecific differences in this ascaroside pheromone language have been described previously, but the genetic basis and molecular mechanisms underlying the variation remain largely unknown. Here, we analyzed natural variation in the production of 44 ascarosides across 95 wild
    MeSH term(s) Animals ; Humans ; Caenorhabditis elegans/genetics ; Pheromones/chemistry ; Genome-Wide Association Study ; Nematoda ; Genetic Variation
    Chemical Substances Pheromones
    Language English
    Publishing date 2023-06-20
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 209104-5
    ISSN 1091-6490 ; 0027-8424
    ISSN (online) 1091-6490
    ISSN 0027-8424
    DOI 10.1073/pnas.2221150120
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

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  4. Article: Evolutionarily related host and microbial pathways regulate fat desaturation.

    Fox, Bennett W / Helf, Maximilian J / Burkhardt, Russell N / Artyukhin, Alexander B / Curtis, Brian J / Palomino, Diana Fajardo / Chaturbedi, Amaresh / Tauffenberger, Arnaud / Wrobel, Chester J J / Zhang, Ying K / Lee, Siu Sylvia / Schroeder, Frank C

    bioRxiv : the preprint server for biology

    2023  

    Abstract: Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase ... ...

    Abstract Fatty acid desaturation is central to metazoan lipid metabolism and provides building blocks of membrane lipids and precursors of diverse signaling molecules. Nutritional conditions and associated microbiota regulate desaturase expression
    Language English
    Publishing date 2023-08-31
    Publishing country United States
    Document type Preprint
    DOI 10.1101/2023.08.31.555782
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Sex-specificity of the C. elegans metabolome.

    Burkhardt, Russell N / Artyukhin, Alexander B / Aprison, Erin Z / Curtis, Brian J / Fox, Bennett W / Ludewig, Andreas H / Palomino, Diana Fajardo / Luo, Jintao / Chaturbedi, Amaresh / Panda, Oishika / Wrobel, Chester J J / Baumann, Victor / Portman, Douglas S / Lee, Siu Sylvia / Ruvinsky, Ilya / Schroeder, Frank C

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 320

    Abstract: Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative ... ...

    Abstract Recent studies of animal metabolism have revealed large numbers of novel metabolites that are involved in all aspects of organismal biology, but it is unclear to what extent metabolomes differ between sexes. Here, using untargeted comparative metabolomics for the analysis of wildtype animals and sex determination mutants, we show that C. elegans hermaphrodites and males exhibit pervasive metabolomic differences. Several hundred small molecules are produced exclusively or in much larger amounts in one sex, including a host of previously unreported metabolites that incorporate building blocks from nucleoside, carbohydrate, lipid, and amino acid metabolism. A subset of male-enriched metabolites is specifically associated with the presence of a male germline, whereas enrichment of other compounds requires a male soma. Further, we show that one of the male germline-dependent metabolites, an unusual dipeptide incorporating N,N-dimethyltryptophan, increases food consumption, reduces lifespan, and accelerates the last stage of larval development in hermaphrodites. Our results serve as a foundation for mechanistic studies of how the genetic sex of soma and germline shape the C. elegans metabolome and provide a blueprint for the discovery of sex-dependent metabolites in other animals.
    MeSH term(s) Animals ; Male ; Caenorhabditis elegans/metabolism ; Metabolome ; Caenorhabditis elegans Proteins/metabolism ; Metabolomics/methods ; Longevity
    Chemical Substances Caenorhabditis elegans Proteins
    Language English
    Publishing date 2023-01-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-36040-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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