Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

Anna Worthmann, Julius Ridder, Sharlaine Y. L. Piel, Ioannis Evangelakos, Melina Musfeldt, Hannah Voß, Marie O’Farrell, Alexander W. Fischer, Sangeeta Adak, Monica Sundd, Hasibullah Siffeti, Friederike Haumann, Katja Kloth, Tatjana Bierhals, Markus Heine, Paul Pertzborn, Mira Pauly, Julia-Josefine Scholz, Suman Kundu, Marceline M. Fuh, Axel Neu, Klaus Tödter, Maja Hempel, Uwe Knippschild, Clay F. Semenkovich, Hartmut Schlüter, Joerg Heeren, Ludger Scheja, Christian Kubisch and Christian Schlein ()
Additional contact information
Anna Worthmann: University Medical Center Hamburg-Eppendorf
Julius Ridder: University Medical Center Hamburg-Eppendorf
Sharlaine Y. L. Piel: University Medical Center Hamburg-Eppendorf
Ioannis Evangelakos: University Medical Center Hamburg-Eppendorf
Melina Musfeldt: University Medical Center Hamburg-Eppendorf
Hannah Voß: University Medical Center Hamburg-Eppendorf
Marie O’Farrell: Sagimet Biosciences Inc.
Alexander W. Fischer: University Medical Center Hamburg-Eppendorf
Sangeeta Adak: Washington University
Monica Sundd: National Institute of Immunology
Hasibullah Siffeti: University Medical Center Hamburg-Eppendorf
Friederike Haumann: University Medical Center Hamburg-Eppendorf
Katja Kloth: University Medical Center Hamburg-Eppendorf
Tatjana Bierhals: University Medical Center Hamburg-Eppendorf
Markus Heine: University Medical Center Hamburg-Eppendorf
Paul Pertzborn: University Medical Center Hamburg-Eppendorf
Mira Pauly: University Medical Center Hamburg-Eppendorf
Julia-Josefine Scholz: University Medical Center Hamburg-Eppendorf
Suman Kundu: University of Delhi South Campus, New Delhi 110021 and Department of Biological Sciences, Birla Institute of Technology and Science Pilani, K K Birla Goa Campus
Marceline M. Fuh: University Medical Center Hamburg-Eppendorf
Axel Neu: University Medical Center Hamburg-Eppendorf
Klaus Tödter: University Medical Center Hamburg-Eppendorf
Maja Hempel: University Medical Center Hamburg-Eppendorf
Uwe Knippschild: University Hospital Ulm
Clay F. Semenkovich: Washington University
Hartmut Schlüter: University Medical Center Hamburg-Eppendorf
Joerg Heeren: University Medical Center Hamburg-Eppendorf
Ludger Scheja: University Medical Center Hamburg-Eppendorf
Christian Kubisch: University Medical Center Hamburg-Eppendorf
Christian Schlein: University Medical Center Hamburg-Eppendorf

Nature Communications, 2024, vol. 15, issue 1, 1-13

Abstract: Abstract Dietary polyunsaturated fatty acids (PUFA) are increasingly recognized for their health benefits, whereas a high production of endogenous fatty acids – a process called de novo lipogenesis (DNL) - is closely linked to metabolic diseases. Determinants of PUFA incorporation into complex lipids are insufficiently understood and may influence the onset and progression of metabolic diseases. Here we show that fatty acid synthase (FASN), the key enzyme of DNL, critically determines the use of dietary PUFA in mice and humans. Moreover, the combination of FASN inhibition and PUFA-supplementation decreases liver triacylglycerols (TAG) in mice fed with high-fat diet. Mechanistically, FASN inhibition causes higher PUFA uptake via the lysophosphatidylcholine transporter MFSD2A, and a diacylglycerol O-acyltransferase 2 (DGAT2)-dependent incorporation of PUFA into TAG. Overall, the outcome of PUFA supplementation may depend on the degree of endogenous DNL and combining PUFA supplementation and FASN inhibition might be a promising approach to target metabolic disease.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/s41467-023-44364-y 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_s41467-023-44364-y

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

DOI: 10.1038/s41467-023-44364-y

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 ().