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

Bennett W. Fox, Maximilian J. Helf, Russell N. Burkhardt, Alexander B. Artyukhin, Brian J. Curtis, Diana Fajardo Palomino, Allen F. Schroeder, Amaresh Chaturbedi, Arnaud Tauffenberger, Chester J. J. Wrobel, Ying K. Zhang, Siu Sylvia Lee and Frank C. Schroeder ()
Additional contact information
Bennett W. Fox: Cornell University
Maximilian J. Helf: Cornell University
Russell N. Burkhardt: Cornell University
Alexander B. Artyukhin: State University of New York
Brian J. Curtis: Cornell University
Diana Fajardo Palomino: Cornell University
Allen F. Schroeder: Cornell University
Amaresh Chaturbedi: Cornell University
Arnaud Tauffenberger: Cornell University
Chester J. J. Wrobel: Cornell University
Ying K. Zhang: Cornell University
Siu Sylvia Lee: Cornell University
Frank C. Schroeder: Cornell University

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-45782-2 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-45782-2

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-45782-2

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().