Nature Communications (Jan 2024)
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,
- Christian Schlein
Affiliations
- Anna Worthmann
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Julius Ridder
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Sharlaine Y. L. Piel
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Ioannis Evangelakos
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Melina Musfeldt
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Hannah Voß
- Section / Core Facility Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
- Marie O’Farrell
- Sagimet Biosciences Inc.
- Alexander W. Fischer
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Sangeeta Adak
- Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University
- Monica Sundd
- National Institute of Immunology
- Hasibullah Siffeti
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Friederike Haumann
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Katja Kloth
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Tatjana Bierhals
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Markus Heine
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Paul Pertzborn
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Mira Pauly
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Julia-Josefine Scholz
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Suman Kundu
- Department of Biochemistry, 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
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Axel Neu
- Department of Pediatrics, University Medical Center Hamburg-Eppendorf
- Klaus Tödter
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Maja Hempel
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Uwe Knippschild
- Department of General and Visceral Surgery, University Hospital Ulm
- Clay F. Semenkovich
- Division of Endocrinology, Metabolism & Lipid Research, Department of Medicine, Washington University
- Hartmut Schlüter
- Section / Core Facility Mass Spectrometry and Proteomics, University Medical Center Hamburg-Eppendorf
- Joerg Heeren
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Ludger Scheja
- Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf
- Christian Kubisch
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- Christian Schlein
- Institute of Human Genetics, University Medical Center Hamburg-Eppendorf
- DOI
- https://doi.org/10.1038/s41467-023-44364-y
- Journal volume & issue
-
Vol. 15,
no. 1
pp. 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.
