Universität zu Köln

Cimen, Ismail, Kocaturk, Begum ORCID: 0000-0003-3657-6055, Koyuncu, Seda, Tufanli, Ozlem, Onat, Umut I., Yildirim, Asli D., Apaydin, Onur, Demirsoy, Seyma, Aykut, Zaliha G., Nguyen, Uyen T., Watkins, Steven M., Hotamisligil, Goekhan S. and Erbay, Ebru ORCID: 0000-0001-9584-1803 (2016). Prevention of atherosclerosis by bioactive palmitoleate through suppression of organelle stress and inflammasome activation. Sci. Transl. Med., 8 (358). WASHINGTON: AMER ASSOC ADVANCEMENT SCIENCE. ISSN 1946-6242

Full text not available from this repository.

Abstract

De 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-1 beta (IL-1 beta) and IL-18 concentrations in vivo in hyperlipidemic mice. Moreover, PAO prevents macrophage ER stress and IL-1 beta 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Cimen, Ismail UNSPECIFIED UNSPECIFIED UNSPECIFIED Kocaturk, Begum UNSPECIFIED orcid.org/0000-0003-3657-6055 UNSPECIFIED Koyuncu, Seda UNSPECIFIED UNSPECIFIED UNSPECIFIED Tufanli, Ozlem UNSPECIFIED UNSPECIFIED UNSPECIFIED Onat, Umut I. UNSPECIFIED UNSPECIFIED UNSPECIFIED Yildirim, Asli D. UNSPECIFIED UNSPECIFIED UNSPECIFIED Apaydin, Onur UNSPECIFIED UNSPECIFIED UNSPECIFIED Demirsoy, Seyma UNSPECIFIED UNSPECIFIED UNSPECIFIED Aykut, Zaliha G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Nguyen, Uyen T. UNSPECIFIED UNSPECIFIED UNSPECIFIED Watkins, Steven M. UNSPECIFIED UNSPECIFIED UNSPECIFIED Hotamisligil, Goekhan S. UNSPECIFIED UNSPECIFIED UNSPECIFIED Erbay, Ebru UNSPECIFIED orcid.org/0000-0001-9584-1803 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-261986
DOI:	10.1126/scitranslmed.aaf9087
Journal or Publication Title:	Sci. Transl. Med.
Volume:	8
Number:	358
Date:	2016
Publisher:	AMER ASSOC ADVANCEMENT SCIENCE
Place of Publication:	WASHINGTON
ISSN:	1946-6242
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language ENDOPLASMIC-RETICULUM STRESS; FATTY-ACID-COMPOSITION; DE-NOVO LIPOGENESIS; BINDING PROTEIN AP2; NLRP3 INFLAMMASOME; ADIPOSE-TISSUE; INSULIN-RESISTANCE; ER STRESS; METABOLIC HOMEOSTASIS; OXIDATIVE STRESS Multiple languages Cell Biology; Medicine, Research & Experimental Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/26198