A Breakthrough in Atherosclerosis Research

Fats are known for their bad health effects, but not all fats. Certain lipids that your body makes can be good for you. A new study that is published in Science Translational Medicine from the laboratory of Asst. Prof. Ebru Erbay of the Department of Molecular Biology and Genetics and UNAM – The National Nanotechnology Research Center at Bilkent University shows that a lipid with unusual physiological effects and made by our bodies can prevent atherosclerosis, when supplied long term via orally.

A monounsaturated fatty acid, palmitoleate (PAO), has been previously associated with improved insulin sensitivity in mice and humans. PAO is not found ubiquitously in most common food sources. However, it can be made by de novo lipogenesis (DNL) in adipocytes and liver. Because DNL and PAO levels increase in obesity and in patients with fatty liver and insulin resistance, it has been incorrectly associated with these disease states. However, previous studies in mice showed that adipose-tissue derived PAO can have important metabolic impact on distant organs; for example, it can improve insulin sensitivity and glucose uptake in muscle while suppressing lipid biogenesis in liver. These studies clearly show PAO has important physiological effects, however, how it operates remained a mystery. In the new study, the lipidomic analysis of tissues obtained from dyslipidemic mice showed that orally delivered PAO enters the cells and integrates into the membranes of intracellular organelles. The dynamic membrane remodeling of a particular organelle, the endoplasmic reticulum (ER), by oral PAO intake had a remarkable impact on the organelle’s functioning. In these mice, the remodeled ER became resilient to stress induced by dyslipidemia. It is known that ER stress contributes to activation of the inflamnasome, a multi-protein complex, which processes a pro-atherogenic cytokine, IL-1b, into its mature, secreted form. Activation of the inflammasome and IL-1b has been causally associated with atherosclerosis as well as insulin resistance and diabetes. Researchers showed that PAO also abolished the activation of inflammasome and suppressed IL-1b in circulation and atherosclerotic plaques. The study findings provide an example of dietary manipulation that can reduce metabolic stress, largely felt at the level of our organelles, and prevent inflammation that drives atherosclerosis.

Erbay Group: Begüm Kocatürk, Buket Gültekin, Özlem Tufanlı, İnci Onat, Ebru Erbay, İsmail Çimen, Onur Apaydın, Pelin Telkoparan

Prevention of Atherosclerosis by Bioactive Palmitoleate Through Suppression of Organelle Stress and Inflammasome Activation

Authors:  Ismail Çimen1.2, Begüm Kocatürk1,2, Seda Koyuncu1, Özlem Tufanlı1.2, Umut I. Onat1.2, Aslı D. Yildirim1,2, Onur Apaydın1,2, Şeyma Demirsoy1 Zaliha G. Aykut1, Uyen T. Nguyen3, Steven M. Watkins3, Gökhan S. Hotamışlıgil4, Ebru Erbay1,2*

Affiliations:

1 Department of Molecular Biology and Genetics, Bilkent University, Ankara 06800, Turkey

2 National Nanotechnology Center, Bilkent University, Ankara 06800, Turkey

3 Metabolon, Sacramento, CA 95691, USA

4 Department of Genetic and Complex Diseases and Sabri Ülker Center, Harvard T.H. Chan School of Public Health, Boston, MA 02115USA

*To whom correspondence should be addressed

*Contact*: Ebru Erbay at +90-(532)3722188 (phone), or eerbay@bilkent.edu.tr

*DOI Information*: Reporters wishing to link to this paper’s abstract on stm.sciencemag.org can use the following URL: http://stm.sciencemag.org/look up/doi/10.1126/scitranslmed.aaf9087

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