Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation

dc.citation.epage393en_US
dc.citation.spage358en_US
dc.citation.volumeNumber8en_US
dc.contributor.authorÇimen, I.en_US
dc.contributor.authorKocatürk, B.en_US
dc.contributor.authorKoyuncu, S.en_US
dc.contributor.authorTufanlı, Ö.en_US
dc.contributor.authorOnat, U. I.en_US
dc.contributor.authorD. Yıldırım, A.en_US
dc.contributor.authorApaydın, O.en_US
dc.contributor.authorDemirsoy, Ş.en_US
dc.contributor.authorG. Aykut, Z.en_US
dc.contributor.authorT. Nguyen, U.en_US
dc.contributor.authorWatkins, S. M.en_US
dc.contributor.authorHotamışlıgil, G. S.en_US
dc.contributor.authorErbay, E.en_US
dc.date.accessioned2019-02-08T07:17:17Z
dc.date.available2019-02-08T07:17:17Z
dc.date.issued2016-09en_US
dc.departmentDepartment of Molecular Biology and Geneticsen_US
dc.departmentInstitute of Materials Science and Nanotechnology (UNAM)en_US
dc.description.abstractDe novo lipogenesis (DNL), the conversion of glucose and other substrates to lipids, is often associated with ectopic lipid accumulation, metabolic stress, and insulin resistance, especially in the liver. However, organ-specific DNL can also generate distinct lipids with beneficial metabolic bioactivity, prompting a great interest in their use for the treatment of metabolic diseases. Palmitoleate (PAO), one such bioactive lipid, regulates lipid metabolism in liver and improves glucose utilization in skeletal muscle when it is generated de novo from the obese adipose tissue. We show that PAO treatment evokes an overall lipidomic remodeling of the endoplasmic reticulum (ER) membranes in macrophages and mouse tissues, which is associated with resistance of the ER to hyperlipidemic stress. By preventing ER stress, PAO blocks lipid-induced inflammasome activation in mouse and human macrophages. Chronic PAO supplementation also lowers systemic interleukin-1β (IL-1β) and IL-18 concentrations in vivo in hyperlipidemic mice. Moreover, PAO prevents macrophage ER stress and IL-1β production in atherosclerotic plaques in vivo, resulting in a marked reduction in plaque macrophages and protection against atherosclerosis in mice. These findings demonstrate that oral supplementation with a product of DNL such as PAO can promote membrane remodeling associated with metabolic resilience of intracellular organelles to lipid stress and limit the progression of atherosclerosis. These findings support therapeutic PAO supplementation as a potential preventive approach against complex metabolic and inflammatory diseases such as atherosclerosis, which warrants further studies in humans.en_US
dc.identifier.doi10.1126/scitranslmed.aaf9087en_US
dc.identifier.issn1946-6234
dc.identifier.urihttp://hdl.handle.net/11693/49100
dc.language.isoEnglishen_US
dc.publisherAmerican Association for the Advancement of Science (AAAS)en_US
dc.relation.isversionofhttps://doi.org/10.1126/scitranslmed.aaf9087en_US
dc.source.titleScience Translational Medicineen_US
dc.titlePrevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activationen_US
dc.typeArticleen_US

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