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Microbial membranes exhibit remarkable diversity in lipid composition, reflecting evolutionary adaptations to various environmental conditions. The three domains of life—Bacteria, Archaea, and Eukarya—synthesize membrane lipids through distinct biosynthetic pathways, leading to fundamental structural differences that impact membrane stability, function, and adaptability.Fatty Acid-Based Lipids in Bacteria and EukaryaBacteria and eukaryotes share a common fatty acid biosynthesis...
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Triglycerides serve as crucial long-term energy storage molecules in microorganisms, providing a dense source of metabolic energy. Their breakdown is mediated by lipases, which hydrolyze triglycerides into glycerol and free fatty acids. Each of these components follows distinct metabolic pathways, ultimately contributing to ATP synthesis and cellular energy homeostasis.Glycerol MetabolismGlycerol, released from triglyceride hydrolysis, is phosphorylated by glycerol kinase to form...
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Lipids also are sources of energy that power cellular processes. Like carbohydrates, lipids are composed of carbon, hydrogen, and oxygen, but these atoms are arranged differently. Most lipids are nonpolar and hydrophobic. Major types include fats and oils, waxes, phospholipids, and steroids.
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Quantitative Determination of De Novo Fatty Acid Synthesis in Brown Adipose Tissue Using Deuterium Oxide
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Evolutionarily related host and microbial pathways regulate fat desaturation.

Bennett W Fox1, Maximilian J Helf1, Russell N Burkhardt1

  • 1Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University, Ithaca, New York 14853, United States.

Biorxiv : the Preprint Server for Biology
|September 11, 2023
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Summary
This summary is machine-generated.

Microbiota and host pathways converge on NHR-49/PPARα to regulate fatty acid desaturation. Small molecules like becyp#1 and bemeth#1 activate fat-7 expression, impacting lipid metabolism.

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Area of Science:

  • Lipid Metabolism
  • Molecular Biology
  • Microbiology

Background:

  • Fatty acid desaturation is crucial for metazoan lipid metabolism, influencing membrane lipids and signaling molecules.
  • Mechanisms by which nutritional conditions and microbiota regulate desaturase expression remain largely unknown.
  • The nuclear receptor NHR-49/PPARα plays a key role in regulating lipid metabolism.

Approach:

  • Utilized untargeted metabolomics in a C. elegans β-oxidation mutant (acdh-11) with constitutively increased stearoyl-CoA desaturase (FAT-7/SCD1) expression.
  • Identified a microbiota-dependent β-cyclopropyl fatty acid (becyp#1) that activates fat-7 expression via NHR-49.
  • Screened for endogenous metabolites and identified a β-methyl fatty acid (bemeth#1) with similar activity, derived from fcmt-1.

Key Points:

  • Microbiota-dependent becyp#1 activates fat-7 expression through NHR-49, requiring bacterial cyclopropane synthase.
  • Endogenous bemeth#1, derived from fcmt-1, mimics becyp#1 activity and likely arose from ancient horizontal gene transfer.
  • Distinct metabolic pathways (β-oxidation for becyp#1, α-oxidation for bemeth#1) control the activation of fat-7 expression by these metabolites.

Conclusions:

  • Host and microbial evolutionarily related pathways converge on NHR-49/PPARα to regulate fat desaturation.
  • Small molecule signals from both host and microbiota play critical roles in modulating lipid metabolism.
  • This study reveals a novel mechanism of host-microbe interaction in regulating essential metabolic processes.