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Related Concept Videos

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Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans.

Bennett W Fox1, Maximilian J Helf1, Russell N Burkhardt1

  • 1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, NY, 14853, USA.

Nature Communications
|February 19, 2024
PubMed
Summary
This summary is machine-generated.

Small molecules from gut bacteria and the host regulate fatty acid desaturation through the NHR-49/PPARα pathway. These signals, including bacterial becyp#1 and endogenous bemeth#1, control lipid metabolism in C. elegans.

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Area of Science:

  • Lipid Metabolism
  • Molecular Biology
  • Microbiology

Background:

  • Fatty acid desaturation is crucial for metazoan membrane lipids and signaling molecules.
  • Mechanisms by which nutrition and microbiota regulate desaturase expression are largely unknown.

Purpose of the Study:

  • To elucidate the mechanisms by which endogenous and microbiota-dependent signals regulate lipid desaturation via the NHR-49/PPARα pathway in C. elegans.

Main Methods:

  • Utilized untargeted metabolomics on a C. elegans beta-oxidation mutant (acdh-11).
  • Investigated the role of cyclopropane synthase in bacterial becyp#1 biosynthesis.
  • Screened for endogenous metabolites mimicking becyp#1 activity, identifying beta-methyl fatty acid (bemeth#1).
  • Analyzed distinct metabolic pathways (beta-oxidation vs. alpha-oxidation) for becyp#1 and bemeth#1.

Main Results:

  • Identified beta-cyclopropyl fatty acid (becyp#1) accumulating in acdh-11 mutants, activating fat-7 expression via NHR-49.
  • Demonstrated becyp#1 biosynthesis is dependent on bacterial cyclopropane synthase.
  • Discovered endogenous bemeth#1, derived from fcmt-1, mimics becyp#1 activity.
  • Showed distinct metabolic fates for becyp#1 (beta-oxidation) and bemeth#1 (alpha-oxidation).

Conclusions:

  • Endogenous and microbiota-derived signals converge on NHR-49/PPARα to regulate fatty acid desaturation.
  • Evolutionarily related pathways in hosts and microbiota coordinate lipid metabolism.
  • Distinct metabolic processing of similar signaling molecules highlights complex regulatory networks.