Khoo Nicholas K H, Schopfer Francisco J
Department of Pharmacology and Chemical Biology, University of Pittsburgh, Pittsburgh, PA, 15213. USA.
Curr Opin Physiol. 2019 Jun;9:67-72. doi: 10.1016/j.cophys.2019.04.013. Epub 2019 Apr 22.
Fatty acids not only provide caloric energy in our diets and building blocks of lipids but are also precursors of potent signaling molecules. Fatty acids can undergo enzymatic and non-enzymatic transformations to form autocrine and paracrine signaling molecules that regulate energy balance and metabolic homeostasis. A new class of lipid signaling mediators known as nitro-fatty acids (NO-FAs) has recently been identified. These NO-FAs are generated endogenously through non-enzymatic reactions of secondary products of nitrite and nitric oxide and are readily detected in human plasma and urine. NO-FAs are potent anti-inflammatory and antioxidant cell signaling mediators and exert protective effects in numerous pre-clinical animal models of disease including cardiovascular, pulmonary and renal fibrosis. Chronic unresolved inflammation is common key feature underlying most fibrotic disorders. Two pathways that converge on inflammation and oxidative stress are nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and nuclear factor kappa B (NF-κB). NO-FAs are pleiotropic signaling modulators that target both of these pathways providing a therapeutic strategy directed towards an integrated decrease in inflammation. This review summarizes the latest findings and understanding of the formation, signaling and anti-fibrotic effects of NO-FA.
脂肪酸不仅在我们的饮食中提供热量能量和脂质的组成成分，还是强效信号分子的前体。脂肪酸可经历酶促和非酶促转化，形成调节能量平衡和代谢稳态的自分泌和旁分泌信号分子。最近发现了一类新的脂质信号介质，称为硝基脂肪酸（NO-FAs）。这些NO-FAs通过亚硝酸盐和一氧化氮的次级产物的非酶促反应内源性产生，并且很容易在人体血浆和尿液中检测到。NO-FAs是强效的抗炎和抗氧化细胞信号介质，在包括心血管、肺和肾纤维化在内的多种临床前疾病动物模型中发挥保护作用。慢性未解决的炎症是大多数纤维化疾病共同的关键特征。两条汇聚于炎症和氧化应激的途径是核因子（红系衍生2）样2（Nrf2）和核因子κB（NF-κB）。NO-FAs是多效性信号调节剂，靶向这两条途径，提供一种针对炎症综合减轻的治疗策略。本综述总结了关于NO-FA的形成、信号传导和抗纤维化作用的最新发现和认识。
