新发现：琥珀酸炎症信号通路信息

由革兰氏阴性细菌产物脂多糖激活的巨噬细胞，核心代谢从氧化磷酸化转化至糖酵解。近日一个研究小组一项成果表明，小鼠巨噬细胞中，2-脱氧葡萄糖对糖酵解的抑制，抑制了脂多糖诱导的白细胞介素-1β（IL-1β），而非肿瘤坏死因子α（TNF-α）。相关研究论文于2013年3月24日在线发表在Nature杂志上。

脂多糖激活的巨噬细胞完整代谢图表明，糖酵解基因表达上调，线粒体基因表达下调，这和代谢产物表达谱相关。脂多糖增加了三羧酸循环中琥珀酸（succinate）的水平。依赖回补反应（anerplerosis）是琥珀酸的主要来源，尽管‘GABA （γ-aminobutyric acid） shunt’ 也发挥一定作用。

脂多糖诱导琥珀酸稳定了缺氧诱导因子-1 ，以IL-1β为靶标，可被2-脱氧葡萄糖抑制。脂多糖也增加的几种蛋白质的琥珀酰化。因此，研究人员确定琥珀酸是先天免疫信号的代谢物，应对炎症过程时，它可以提高白细胞介素-1β的产量

原文摘要：

Succinate is an inflammatory signal that induces IL-1β through HIF-1α

Macrophages activated by the Gram-negative bacterial product lipopolysaccharide switch their core metabolism from oxidative phosphorylation to glycolysis1. Here we show that inhibition of glycolysis with 2-deoxyglucose suppresses lipopolysaccharide-induced interleukin-1β but not tumour-necrosis factor-α in mouse macrophages. A comprehensive metabolic map of lipopolysaccharide-activated macrophages shows upregulation of glycolytic and downregulation of mitochondrial genes, which correlates directly with the expression profiles of altered metabolites. Lipopolysaccharide strongly increases the levels of the tricarboxylic-acid cycle intermediate succinate. Glutamine-dependent anerplerosis is the principal source of succinate, although the ‘GABA （γ-aminobutyric acid） shunt’ pathway also has a role. Lipopolysaccharide-induced succinate stabilizes hypoxia-inducible factor-1α, an effect that is inhibited by 2-deoxyglucose, with interleukin-1β as an important target. Lipopolysaccharide also increases succinylation of several proteins. We therefore identify succinate as a metabolite in innate immune signalling, which enhances interleukin-1β