Instituto de Biología y Genética Molecular, Consejo Superior de Investigaciones Científicas, 47003 Valladolid and the Centro de Investigación Biomédica en Red de Diabetes y Enfermedades Metabólicas Asociadas, 08036 Barcelona, Spain.
J Biol Chem. 2012 Mar 30;287(14):10894-904. doi: 10.1074/jbc.M112.342915. Epub 2012 Feb 8.
Lipin-2 is a member of the lipin family of enzymes, which are key effectors in the biosynthesis of lipids. Mutations in the human lipin-2 gene are associated with inflammatory-based disorders; however, the role of lipin-2 in cells of the immune system remains obscure. In this study, we have investigated the role of lipin-2 in the proinflammatory action of saturated fatty acids in murine and human macrophages. Depletion of lipin-2 promotes the increased expression of the proinflammatory genes Il6, Ccl2, and Tnfα, which depends on the overstimulation of the JNK1/c-Jun pathway by saturated fatty acids. In contrast, overexpression of lipin-2 reduces the release of proinflammatory factors. Metabolically, the absence of lipin-2 reduces the cellular content of triacylglycerol in saturated fatty acid-overloaded macrophages. Collectively, these studies demonstrate a protective role for lipin-2 in proinflammatory signaling mediated by saturated fatty acids that occurs concomitant with an enhanced cellular capacity for triacylglycerol synthesis. The data provide new insights into the role of lipin-2 in human and murine macrophage biology and may open new avenues for controlling the fatty acid-related low grade inflammation that constitutes the sine qua non of obesity and associated metabolic disorders.
脂联素-2 是脂联素家族酶的成员，是脂质生物合成的关键效应物。人类脂联素-2 基因的突变与炎症为基础的疾病有关；然而，脂联素-2 在免疫系统细胞中的作用仍然不清楚。在这项研究中，我们研究了脂联素-2 在饱和脂肪酸诱导的小鼠和人巨噬细胞炎症反应中的作用。脂联素-2 的耗竭促进了促炎基因 Il6、Ccl2 和 Tnfα 的表达增加，这依赖于饱和脂肪酸对 JNK1/c-Jun 途径的过度刺激。相比之下，脂联素-2 的过表达减少了促炎因子的释放。在代谢上，脂联素-2 的缺失减少了饱和脂肪酸超负荷巨噬细胞中三酰甘油的细胞含量。总的来说，这些研究表明脂联素-2 在饱和脂肪酸介导的促炎信号中发挥保护作用，同时增强了细胞合成三酰甘油的能力。这些数据为脂联素-2 在人类和小鼠巨噬细胞生物学中的作用提供了新的见解，并可能为控制与肥胖和相关代谢紊乱相关的脂肪酸相关低度炎症开辟新的途径。
