The Arachidonic Acid Metabolome Serves as a Conserved Regulator of Cholesterol Metabolism
- Demetz, Egon
- Schroll, Andrea
- Auer, Kristina
- Heim, Christiane
- Patsch, Josef R.
- Eller, Philipp
- Theurl, Markus
- Theurl, Igor
- Theurl, Milan
- Seifert, Markus
- Lener, Daniela
- Stanzl, Ursula
- Haschka, David
- Asshoff, Malte
- Dichtl, Stefanie
- Nairz, Manfred
- Huber, Eva
- Stadlinger, Martin
- Moschen, Alexander R.
- Li, Xiaorong
- Pallweber, Petra
- Scharnagl, Hubert
- Stojakovic, Tatjana
- März, Winfried
- Kleber, Marcus E.
- Garlaschelli, Katia
- Uboldi, Patrizia
- Catapano, Alberico L.
- Stellaard, Frans
- Rudling, Mats
- Kuba, Keiji
- Imai, Yumiko
- Arita, Makoto
- Schuetz, John D.
- Pramstaller, Peter P.
- Tietge, Uwe J.F.
- Trauner, Michael
- Norata, Giuseppe D.
- Claudel, Thierry
- Hicks, Andrew A.
- Weiss, Guenter
- Tancevski, Ivan
DOIAbstract
SummaryCholesterol metabolism is closely interrelated with cardiovascular disease in humans. Dietary supplementation with omega-6 polyunsaturated fatty acids including arachidonic acid (AA) was shown to favorably affect plasma LDL-C and HDL-C. However, the underlying mechanisms are poorly understood. By combining data from a GWAS screening in >100,000 individuals of European ancestry, mediator lipidomics, and functional validation studies in mice, we identify the AA metabolome as an important regulator of cholesterol homeostasis. Pharmacological modulation of AA metabolism by aspirin induced hepatic generation of leukotrienes (LTs) and lipoxins (LXs), thereby increasing hepatic expression of the bile salt export pump Abcb11. Induction of Ab...
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