Occurrence and biological activity of palmitoleic acid isomers in phagocytic cells

Abstract

Recent studies have highlighted the role of palmitoleic acid [16:1 (-9-hexadecenoic acid)] as a lipid hormone that coordinates cross-talk between liver and adipose tissue and exerts anti-inflammatory protective effects on hepatic steatosis and insulin signaling in murine models of metabolic disease. More recently, a 16:1 isomer, -7-hexadecenoic acid (16:1), that also possesses marked anti-inflammatory effects, has been described in human circulating monocytes and monocyte-derived macrophages. By using gas chromatographic/mass spectrometric analyses of dimethyl disulfide derivatives of fatty acyl methyl esters, we describe in this study the presence of a third 16:1 isomer, sapienic acid [16:1 (6--hexadecenoic acid)], in phagocytic cells. Cellular levels of 16:1 appear to depend not only on the cellular content of linoleic acid, but also on the expression level of fatty acid desaturase 2, thus revealing a complex regulation both at the enzyme level, via fatty acid substrate competition, and directly at the gene level. However, unlike 16:1 and 16:1, 16:1 levels are not regulated by the activation state of the cell. Moreover, while 16:1 and 16:1 manifest strong anti-inflammatory activity when added to the cells at low concentrations (10 μM), notably higher concentrations of 16:1 are required to observe a comparable effect. Collectively, these results suggest the presence in phagocytic cells of an unexpected variety of 16:1 isomers, which can be distinguished on the basis of their biological activity and cellular regulation.

Comprehensive analysis of PPARγ agonist activities of stereo-, regio-, and enantio-isomers of hydroxyoctadecadienoic acids

“…The structural features of some lipids affect their biological activity in vivo. For example, palmitoleic acid isomers (16:1n−7, 16:1n−9, 16:1n−10) manifest anti-inflammatory activity at different concentrations in phagocytic cells [11]. Our findings also led to the speculation that physiological activities are divergent among HODE isomers, because the levels of only 10and 12-(Z,E)-HODEs are correlated with plasma glucose level in the prediabetic state [6,7].…”

The Contribution of Cytosolic Group IVA and Calcium-Independent Group VIA Phospholipase A2s to Adrenic Acid Mobilization in Murine Macrophages

“…Arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid, AA), a fatty acid of the n-6 series, is the major polyunsaturated fatty acid present in cells of the innate immunity [1]. Cleavage of AA-containing membrane phospholipids by phospholipase A 2 (PLA 2 ) enzymes during activation results in substantial release of free AA.…”

“…Innate immune cells also contain significant quantities of another n-6 fatty acid, adrenic acid (cis-7,10,13,16-docosatetraenoic acid, AdA), which is the 2-carbon elongation product of AA [1] Recent work from our laboratory has taken advantage of mass-spectrometry-based lipidomic approaches to define at a molecular level the mechanisms regulating AA mobilization from phagocytic cells responding to stimuli of the innate immune response [17][18][19][20][21][22][23][24][25][26][27]. Our work has highlighted not only the importance of multiple PLA2 enzymes in the process, but also of the mechanisms regulating the reacylation of the liberated fatty acid back into phospholipids and the remodeling that places the AA in the appropriate cellular lipid pools.…”

Phospholipid arachidonic acid remodeling in macrophages: role of plasmalogen species

“…According to the above results (Figures 15 and 16) and to other studies (229,230), cell lines exhibit diminished levels of PUFAs compared to normal cells. Specifically, RAW264.7 cells contain 2-3-fold less AA than RPMs (219). This AA deficiency in RAW264.7 cells could cause faster remodeling compared to normal macrophages.…”

“…FAMEs were obtained from the various lipid fractions by transmethylation with 0.5 M KOH in methanol for 60 min at 37 ºC (215,(217)(218)(219)(220). Analysis was carried out using an Agilent 7890A gas chromatograph coupled to an Agilent 5975C mass-selective detector operated in electron impact mode (EI, 70 eV), equipped with an Agilent 7693 autosampler and an Agilent DB23 column (60 m length x 0.25 mm internal diameter x 0.15 µm film thickness).…”