TY - JOUR
T1 - Double bond configuration of palmitoleate is critical for atheroprotection
AU - Cimen, Ismail
AU - Yildirim, Zehra
AU - Dogan, Asli Ekin
AU - Yildirim, Asli Dilber
AU - Tufanli, Ozlem
AU - Onat, Umut Inci
AU - UyenThao Nguyen, null
AU - Watkins, Steven M.
AU - Weber, Christian
AU - Erbay, Ebru
N1 - Funding Information:
We express our appreciation to Alexander Bartelt (Ludwig Maximillians University) for critical reading of the manuscript, Peter Walter (University of California, San Francisco) for providing the GFP-IRE1 and KDEL plasmids, and Metabolon for lipidomic analysis. This work was supported by a Marie Curie Reintegration Grant (Lipokines – 276922 ) to EE and European Research Council AdG ° 692511 to CW.
Funding Information:
We express our appreciation to Alexander Bartelt (Ludwig Maximillians University) for critical reading of the manuscript, Peter Walter (University of California, San Francisco) for providing the GFP-IRE1 and KDEL plasmids, and Metabolon for lipidomic analysis. This work was supported by a Marie Curie Reintegration Grant (Lipokines ? 276922) to EE and European Research Council AdG ?692511 to CW.
Publisher Copyright:
© 2019 The Authors
PY - 2019/10
Y1 - 2019/10
N2 - 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. (C) 2019 The Authors. Published by Elsevier GmbH.
AB - 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. (C) 2019 The Authors. Published by Elsevier GmbH.
KW - Lipid-induced inflammation
KW - Lipokines
KW - Palmitoleate
KW - Ruminant trans-fatty acids
KW - Organelle stress
KW - Inflammasome
KW - Atherosclerosis
KW - TRANS-FATTY-ACIDS
KW - ENDOPLASMIC-RETICULUM STRESS
KW - UNFOLDED PROTEIN RESPONSE
KW - NLRP3 INFLAMMASOME
KW - DAIRY FAT
KW - ER STRESS
KW - EXPERIMENTAL ATHEROSCLEROSIS
KW - UNSATURATED FATS
KW - ADIPOSE-TISSUE
KW - RISK
U2 - 10.1016/j.molmet.2019.08.004
DO - 10.1016/j.molmet.2019.08.004
M3 - Article
C2 - 31422082
SN - 2212-8778
VL - 28
SP - 58
EP - 72
JO - Molecular Metabolism
JF - Molecular Metabolism
ER -