Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use
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Published:2024-01-02
Issue:1
Volume:15
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Worthmann Anna, Ridder Julius, Piel Sharlaine Y. L., Evangelakos IoannisORCID, Musfeldt Melina, Voß Hannah, O’Farrell Marie, Fischer Alexander W.ORCID, Adak Sangeeta, Sundd Monica, Siffeti Hasibullah, Haumann Friederike, Kloth Katja, Bierhals Tatjana, Heine Markus, Pertzborn Paul, Pauly Mira, Scholz Julia-Josefine, Kundu SumanORCID, Fuh Marceline M., Neu Axel, Tödter Klaus, Hempel MajaORCID, Knippschild UweORCID, Semenkovich Clay F.ORCID, Schlüter HartmutORCID, Heeren JoergORCID, Scheja Ludger, Kubisch Christian, Schlein ChristianORCID
Abstract
AbstractDietary 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
Reference64 articles.
1. Postic, C. & Girard, J. Contribution of de novo fatty acid synthesis to hepatic steatosis and insulin resistance: lessons from genetically engineered mice. J. Clin. Invest. 118, 829–838 (2008). 2. Perry, R. J., Samuel, V. T., Petersen, K. F. & Shulman, G. I. The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510, 84–91 (2014). 3. Chong, M. F., Fielding, B. A. & Frayn, K. N. Metabolic interaction of dietary sugars and plasma lipids with a focus on mechanisms and de novo lipogenesis. Proc. Nutr. Soc. 66, 52–59 (2007). 4. Palmisano, B. T., Zhu, L. & Stafford, J. M. Role of estrogens in the regulation of liver lipid metabolism. Adv. Exp. Med. Biol. 1043, 227–256 (2017). 5. Yao, X. et al. Regulation of fatty acid composition and lipid storage by thyroid hormone in mouse liver. Cell Biosci. 4, 38 (2014).
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