Fatty Acid Synthesis Suppresses Dietary Polyunsaturated Fatty Acid Use

Overview

Journal Nat Commun

Specialty Biology

Date 2024 Jan 3

PMID 38167725

Authors

Anna Worthmann

Julius Ridder

Sharlaine Y L Piel

Ioannis Evangelakos

Melina Musfeldt

Hannah Voss

Marie OFarrell

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 Todter

Maja Hempel

Uwe Knippschild

Clay F Semenkovich

Hartmut Schluter

Joerg Heeren

Ludger Scheja

Christian Kubisch

Christian Schlein

Affiliations

Soon will be listed here.

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.

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