Abstract：
Recent advances in fatty acid analysis have highlighted the links between lipid disruption and disease development. Lipid abnormalities are well-established risk factors for many of the most common chronic illnesses, and their involvement in asthma is also becoming clear. Here, we review research demonstrating the role of abnormal lipid metabolism in asthma, with a focus on saturated fatty acids and sphingolipids. High levels of palmitic acid, the most abundant saturated fatty acid in the human body, have been found in the airways of asthmatic patients with obesity, and were shown to worsen eosinophilic airway inflammation in asthma model mice on a high-fat diet. Aside from being a building block of longer-chain fatty acids, palmitic acid is also the starting point for de novo synthesis of ceramides, a class of sphingolipids. We outline the three main pathways for the synthesis of ceramides, which have been linked to the severity of asthma and act as precursors for the dynamic lipid mediator sphingosine 1-phosphate (S1P). S1P signaling is involved in allergen-induced eosinophilic inflammation, airway hyperresponsiveness, and immune-cell trafficking. A recent study of mice with mutations for the elongation of very long-chain fatty acid family member 6 (Elovl6), an enzyme that elongates fatty acid chains, has highlighted the potential role of palmitic acid composition, and thus lipid balance, in the pathophysiology of allergic airway inflammation. Elovl6 may be a potential therapeutic target in severe asthma.
摘要：
脂肪酸分析的最新进展突出了脂质破坏与疾病发展之间的联系。脂质异常是许多最常见的慢性疾病的公认危险因素，它们与哮喘的关系也变得越来越明显。这里,我们回顾了脂质代谢异常在哮喘中的作用，专注于饱和脂肪酸和鞘脂。高含量的棕榈酸,人体内最丰富的饱和脂肪酸，已经在肥胖的哮喘患者的气道中发现，并显示在高脂饮食的哮喘模型小鼠中恶化嗜酸性粒细胞气道炎症。除了是长链脂肪酸的组成部分，棕榈酸也是从头合成神经酰胺的起点，一类鞘脂。我们概述了合成神经酰胺的三种主要途径，与哮喘的严重程度有关，并作为动态脂质介质1-磷酸鞘氨醇（S1P）的前体。S1P信号参与过敏原诱导的嗜酸性粒细胞炎症，气道高反应性,和免疫细胞贩运。最近对具有非常长链脂肪酸家族成员6（Elovl6）的延伸突变的小鼠的研究，一种延长脂肪酸链的酶，强调了棕榈酸成分的潜在作用，因此脂质平衡，在过敏性气道炎症的病理生理学中。Elovl6可能是严重哮喘的潜在治疗靶点。
