Occurrence and biological activity of palmitoleic acid isomers in phagocytic cells

Recent studies have highlighted the role of palmitoleic acid [16: 1n-7 (cis-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: 1n-7 isomer, cis-7-hexadecenoic acid (16: 1n-9), 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: 1n-10 (6-cis-hexadecenoic acid)], in phagocytic cells. Cellular levels of 16: 1n-10 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: 1n-7 and 16: 1n-9, 16: 1n-10 levels are not regulated by the activation state of the cell. Moreover, while 16: 1n-7 and 16: 1n-9 manifest strong anti-inflammatory activity when added to the cells at low concentrations (10 mu M), notably higher concentrations of 16: 1n-10 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.