Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use

被引：13

作者：

Worthmann, Anna ^{[1
]}

Ridder, Julius ^{[2
]}

Piel, Sharlaine Y. L. ^{[2
]}

Evangelakos, Ioannis ^{[2
]}

Musfeldt, Melina ^{[2
]}

Voss, Hannah ^{[3
]}

O'Farrell, Marie ^{[4
]}

Fischer, Alexander W. ^{[1
,5
,6
]}

Adak, Sangeeta ^{[7
]}

Sundd, Monica ^{[8
]}

Siffeti, Hasibullah ^{[2
]}

Haumann, Friederike ^{[2
]}

Kloth, Katja ^{[2
]}

Bierhals, Tatjana ^{[2
]}

Heine, Markus ^{[1
]}

Pertzborn, Paul ^{[1
]}

Pauly, Mira ^{[1
]}

Scholz, Julia-Josefine ^{[2
]}

Kundu, Suman ^{[9
,10
]}

Fuh, Marceline M. ^{[1
]}

Neu, Axel ^{[11
]}

Toedter, Klaus ^{[1
]}

Hempel, Maja ^{[2
,12
]}

Knippschild, Uwe ^{[13
]}

Semenkovich, Clay F. ^{[7
]}

Schlueter, Hartmut ^{[3
]}

Heeren, Joerg ^{[1
]}

Scheja, Ludger ^{[1
]}

Kubisch, Christian ^{[2
]}

Schlein, Christian ^{[2
]}

机构：

[1] Univ Med Ctr Hamburg Eppendorf, Dept Biochem & Mol Cell Biol, Hamburg, Germany

[2] Univ Med Ctr Hamburg Eppendorf, Inst Human Genet, Hamburg, Germany

[3] Univ Med Ctr Hamburg Eppendorf, Sect Core Facil Mass Spectrometry & Prote, Hamburg, Germany

[4] Sagimet Biosci Inc, 155 Bovet Rd, San Mateo, CA 94402 USA

[5] Harvard Univ, Harvard T H Chan Sch Publ Hlth, Dept Mol Metab, Boston, MA USA

[6] Harvard Med Sch, Dept Cell Biol, Boston, MA USA

[7] Washington Univ, Dept Med, Div Endocrinol Metab & Lipid Res, St Louis, MO USA

[8] Natl Inst Immunol, New Delhi, India

[9] Univ Delhi South Campus, Dept Biochem, New Delhi 110021, India

[10] Birla Inst Technol & Sci Pilani, Dept Biol Sci, K K Birla Goa Campus, Pilani 403726, Goa, India

[11] Univ Med Ctr Hamburg Eppendorf, Dept Pediat, Hamburg, Germany

[12] Univ Hosp Heidelberg, Inst Human Genet, Neuenheimer Feld 440, D-69120 Heidelberg, Germany

[13] Univ Hosp Ulm, Dept Gen & Visceral Surg, Ulm, Germany

来源：

NATURE COMMUNICATIONS | 2024年 / 15卷 / 01期

关键词：

DE-NOVO LIPOGENESIS; HEPATIC STEATOSIS; INSULIN-RESISTANCE; ADIPOSE-TISSUE; PLASMA TRIGLYCERIDES; LIVER-DISEASE; UP-REGULATION; LIPIDS; UBIQUITINATION; LIPOPROTEINS;

D O I：

10.1038/s41467-023-44364-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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. Polyunsaturated Fatty Acids (PUFA), such as omega-3 fatty acids, are recognized for their lipid lowering and anti-inflammatory properties. Here, the authors show that endogenous lipid synthesis controls the use of PUFA and thus determine the therapeutic benefit of omega-3 fatty acid supplementation.

引用

页数：13

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