Hardwick James P, Eckman Katie, Lee Yoon Kwang, Abdelmegeed Mohamed A, Esterle Andrew, Chilian William M, Chiang John Y, Song Byoung-Joon
Biochemistry and Molecular Pathology, Department of Integrative Medical Sciences, Northeast Ohio Medical University, Rootstown, Ohio, USA.
Adv Pharmacol. 2013;66:157-266. doi: 10.1016/B978-0-12-404717-4.00005-6.
Chronic persistent inflammation plays a significant role in disease pathology of cancer, cardiovascular disease, and metabolic syndrome (MetS). MetS is a constellation of diseases that include obesity, diabetes, hypertension, dyslipidemia, hypertriglyceridemia, and hypercholesterolemia. Nonalcoholic fatty liver disease (NAFLD) is associated with many of the MetS diseases. These metabolic derangements trigger a persistent inflammatory cascade, which includes production of lipid autacoids (eicosanoids) that recruit immune cells to the site of injury and subsequent expression of cytokines and chemokines that amplify the inflammatory response. In acute inflammation, the transcellular synthesis of antiinflammatory eicosanoids resolve inflammation, while persistent activation of the autacoid-cytokine-chemokine cascade in metabolic disease leads to chronic inflammation and accompanying tissue pathology. Many drugs targeting the eicosanoid pathways have been shown to be effective in the treatment of MetS, suggesting a common linkage between inflammation, MetS and drug metabolism. The cross-talk between inflammation and MetS seems apparent because of the growing evidence linking immune cell activation and metabolic disorders such as insulin resistance, dyslipidemia, and hypertriglyceridemia. Thus modulation of lipid metabolism through either dietary adjustment or selective drugs may become a new paradigm in the treatment of metabolic disorders. This review focuses on the mechanisms linking eicosanoid metabolism to persistent inflammation and altered lipid and carbohydrate metabolism in MetS.
慢性持续性炎症在癌症、心血管疾病和代谢综合征（MetS）的疾病病理过程中起着重要作用。代谢综合征是一组包括肥胖、糖尿病、高血压、血脂异常、高甘油三酯血症和高胆固醇血症的疾病。非酒精性脂肪性肝病（NAFLD）与许多代谢综合征疾病相关。这些代谢紊乱引发持续的炎症级联反应，其中包括脂质自分泌调节因子（类花生酸）的产生，这些因子会将免疫细胞招募到损伤部位，随后细胞因子和趋化因子表达，放大炎症反应。在急性炎症中，抗炎类花生酸的跨细胞合成可消除炎症，而代谢性疾病中自分泌调节因子 - 细胞因子 - 趋化因子级联反应的持续激活会导致慢性炎症及伴随的组织病理变化。许多靶向类花生酸途径的药物已被证明对代谢综合征的治疗有效，这表明炎症、代谢综合征和药物代谢之间存在共同联系。由于越来越多的证据表明免疫细胞激活与胰岛素抵抗、血脂异常和高甘油三酯血症等代谢紊乱之间存在联系，炎症与代谢综合征之间的相互作用似乎很明显。因此，通过饮食调整或选择性药物调节脂质代谢可能成为治疗代谢紊乱的新范例。本综述重点关注类花生酸代谢与代谢综合征中持续炎症以及脂质和碳水化合物代谢改变之间的联系机制。
