Double bond configuration of palmitoleate is critical for atheroprotection

Abstract

ObjectiveSaturated 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.MethodsUsing 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.ResultsOral 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.ConclusionsA 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.

Polarization of Macrophages in Human Adipose Tissue is Related to the Fatty Acid Spectrum in Membrane Phospholipids

“…All the beneficial effects of palmitoleate do not correspond to its stimulation of proinflammatory polarization in human adipose tissue in our data. This discrepancy could be explained by the substantially different effect of cis-and trans-palmitoleate reported recently [32].…”

The Regulation of Lipokines by Environmental Factors

“…The double bond of palmitoleate, known as cis- palmitoleate or trans-palmitoleate, is essential for atherosclerosis protection. Only the cis-palmitoleate conformation reduces ER-stress and inflammation, while the trans-conformation does not [87]. The supplementation of PAO increases the rate of ER membrane-lipid remodeling in macrophages and other tissues, which prevents the lipid-mediated activation of the inflammasome and prevents activation of pro-inflammatory cells [86].…”

Cow's milk: Composition, nutritional, biological and cardioprotective benefits

“…Les produits laitiers sont souvent considérés comme délétères sur le plan du risque cardiovasculaire (RCV). Or, les études épidémiologiques sont loin d'être négatives, tant sur la base des enquêtes alimentaires que des biomarqueurs [1][2][3][4][5][6]. En effet, les données scientifiques (épidémiologiques, cliniques et mécanistiques) sont en faveur d'un rôle bénéfique du lait et de ses dérivés en terme de RCV [3][4][5], puisque certains de ces résultats concernant, par exemple, le diabète de type 2 (DT2) et le syndrome métabolique (SMet) sont en faveur d'un effet protecteur [7,8].…”