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      Double bond configuration of palmitoleate is critical for atheroprotection

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      Author(s)
      Çimen, I.
      Yıldırım, Zehra
      Doğan, Aslı Ekin
      Yıldırım, Aslı Dilber
      Tufanlı, Ö.
      Onat, Umut İnci
      Nguyen, U.
      Watkins, S.
      Weber, C.
      Erbay, Ebru
      Date
      2019
      Source Title
      Molecular Metabolism
      Print ISSN
      2212-8778
      Publisher
      Elsevier
      Volume
      28
      Pages
      58 - 72
      Language
      English
      Type
      Article
      Item Usage Stats
      137
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      87
      downloads
      Abstract
      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
      Permalink
      http://hdl.handle.net/11693/53092
      Published Version (Please cite this version)
      https://dx.doi.org/10.1016/j.molmet.2019.08.004
      Collections
      • Department of Molecular Biology and Genetics 512
      • Nanotechnology Research Center (NANOTAM) 1125
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