Double bond configuration of palmitoleate is critical for atheroprotection

Ismail Cimen; Zehra Yildirim; Asli Ekin Dogan; Asli Dilber Yildirim; Ozlem Tufanli; Umut Inci Onat; UyenThao Nguyen; Steven M. Watkins; Christian Weber; Ebru Erbay

Molecular Metabolism (Oct 2019)

Double bond configuration of palmitoleate is critical for atheroprotection

Ismail Cimen,
Zehra Yildirim,
Asli Ekin Dogan,
Asli Dilber Yildirim,
Ozlem Tufanli,
Umut Inci Onat,
UyenThao Nguyen,
Steven M. Watkins,
Christian Weber,
Ebru Erbay

Affiliations

Ismail Cimen: Institute for Cardiovascular Prevention, LMU Munich, German Cardiovascular Research Centre (DZHK), Partner Site Munich Heart Alliance Munich, 80336, Germany
Zehra Yildirim: Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800, Turkey; National Nanotechnology Center, Bilkent University, Ankara, 06800, Turkey; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
Asli Ekin Dogan: Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800, Turkey; National Nanotechnology Center, Bilkent University, Ankara, 06800, Turkey; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
Asli Dilber Yildirim: Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800, Turkey; National Nanotechnology Center, Bilkent University, Ankara, 06800, Turkey; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA
Ozlem Tufanli: New York University, Lagone Medical Center, New York, NY 10016, USA
Umut Inci Onat: Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800, Turkey; National Nanotechnology Center, Bilkent University, Ankara, 06800, Turkey
UyenThao Nguyen: Metabolon, Morrisville, NC, 27560, USA
Steven M. Watkins: Verso Biosciences, San Francisco, CA, 94124, USA
Christian Weber: Institute for Cardiovascular Prevention, LMU Munich, German Cardiovascular Research Centre (DZHK), Partner Site Munich Heart Alliance Munich, 80336, Germany; Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands
Ebru Erbay: Department of Molecular Biology and Genetics, Bilkent University, Ankara, 06800, Turkey; National Nanotechnology Center, Bilkent University, Ankara, 06800, Turkey; Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; Smidt Heart Institute, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA; David Geffen School of Medicine, University of California, Los Angeles, CA, 90095, USA; Corresponding author. Cedars Sinai Medical Center, Department of Medicine, Heart Institute & Department of Biomedical Sciences, 127 S. San Vincente Boulevard, Advanced Health Sciences Pavillion, A9104, Los Angeles, CA, 90048, USA.

Journal volume & issue: Vol. 28
pp. 58 – 72

Abstract

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Objective: Saturated and trans fat consumption is associated with increased cardiovascular disease (CVD) risk. Current dietary guidelines recommend low fat and significantly reduced trans fat intake. Full fat dairy can worsen dyslipidemia, but recent epidemiological studies show full-fat dairy consumption may reduce diabetes and CVD risk. This dairy paradox prompted a reassessment of the dietary guidelines. The beneficial metabolic effects in dairy have been claimed for a ruminant-derived, trans fatty acid, trans-C16:1n-7 or trans-palmitoleate (trans-PAO). A close relative, cis-PAO, is produced by de novo lipogenesis and mediates inter-organ crosstalk, improving insulin-sensitivity and alleviating atherosclerosis in mice. These findings suggest trans-PAO may be a useful substitute for full fat dairy, but a metabolic function for trans-PAO has not been shown to date. Methods: Using lipidomics, we directly investigated trans-PAO's impact on plasma and tissue lipid profiles in a hypercholesterolemic atherosclerosis mouse model. Furthermore, we investigated trans-PAO's impact on hyperlipidemia-induced inflammation and atherosclerosis progression in these mice. Results: Oral trans-PAO supplementation led to significant incorporation of trans-PAO into major lipid species in plasma and tissues. Unlike cis-PAO, however, trans-PAO did not prevent organelle stress and inflammation in macrophages or atherosclerosis progression in mice. Conclusions: A significant, inverse correlation between circulating trans-PAO levels and diabetes incidence and cardiovascular mortality has been reported. Our findings show that trans-PAO can incorporate efficiently into the same pools that its cis counterpart is known to incorporate into. However, we found trans-PAO's anti-inflammatory and anti-atherosclerotic effects are muted due to its different structure from cis-PAO. Keywords: Lipid-induced inflammation, Lipokines, Palmitoleate, Ruminant trans-fatty acids, Organelle stress, Inflammasome, Atherosclerosis

Published in Molecular Metabolism

ISSN: 2212-8778 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Medicine: Internal medicine
Website: https://www.journals.elsevier.com/molecular-metabolism/

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