Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use
Standard
Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use. / Worthmann, Anna; Ridder, Julius; Piel, Sharlaine Y L; Evangelakos, Ioannis; Musfeldt, Melina; Voß, Hannah; O'Farrell, Marie; Fischer, Alexander W; Adak, Sangeeta; Sundd, Monica; Siffeti, Hasibullah; Haumann, Friederike; Kloth, Katja; Bierhals, Tatjana; Heine, Markus; Pertzborn, Paul; Pauly, Mira; Scholz, Julia-Josefine; Kundu, Suman; Fuh, Marceline M; Neu, Axel; Tödter, Klaus; Hempel, Maja; Knippschild, Uwe; Semenkovich, Clay F; Schlüter, Hartmut; Heeren, Joerg; Scheja, Ludger; Kubisch, Christian; Schlein, Christian.
in: NAT COMMUN, Jahrgang 15, Nr. 1, 02.01.2024, S. 45.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
Harvard
APA
Vancouver
Bibtex
}
RIS
TY - JOUR
T1 - Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use
AU - Worthmann, Anna
AU - Ridder, Julius
AU - Piel, Sharlaine Y L
AU - Evangelakos, Ioannis
AU - Musfeldt, Melina
AU - Voß, Hannah
AU - O'Farrell, Marie
AU - Fischer, Alexander W
AU - Adak, Sangeeta
AU - Sundd, Monica
AU - Siffeti, Hasibullah
AU - Haumann, Friederike
AU - Kloth, Katja
AU - Bierhals, Tatjana
AU - Heine, Markus
AU - Pertzborn, Paul
AU - Pauly, Mira
AU - Scholz, Julia-Josefine
AU - Kundu, Suman
AU - Fuh, Marceline M
AU - Neu, Axel
AU - Tödter, Klaus
AU - Hempel, Maja
AU - Knippschild, Uwe
AU - Semenkovich, Clay F
AU - Schlüter, Hartmut
AU - Heeren, Joerg
AU - Scheja, Ludger
AU - Kubisch, Christian
AU - Schlein, Christian
N1 - © 2024. The Author(s).
PY - 2024/1/2
Y1 - 2024/1/2
N2 - 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.
AB - 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.
KW - Mice
KW - Humans
KW - Animals
KW - Lipogenesis
KW - Fatty Acids, Omega-3/pharmacology
KW - Fatty Acids, Unsaturated
KW - Triglycerides/metabolism
KW - Fatty Acids
KW - Diet, High-Fat/adverse effects
KW - Metabolic Diseases
U2 - 10.1038/s41467-023-44364-y
DO - 10.1038/s41467-023-44364-y
M3 - SCORING: Journal article
C2 - 38167725
VL - 15
SP - 45
JO - NAT COMMUN
JF - NAT COMMUN
SN - 2041-1723
IS - 1
ER -