Docosahexaenoic Acid-Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties
Docosahexaenoic Acid-Derived Fatty Acid Esters of Hydroxy Fatty Acids (FAHFAs) With Anti-inflammatory Properties
复制标题
DOI：
10.2337/db16-0385
复制
发表时间：
2016-09-01
期刊：
影响因子：
7.7
通讯作者：
Kopecky, Jan
中科院分区：
文献类型：
--
作者：
Kuda, Ondrej;Brezinova, Marie;Kopecky, Jan
白色脂肪组织是一种兼具代谢和内分泌功能的复杂器官。WAT所有这些功能的失调，加上肥胖者组织的轻度炎症，都会导致胰岛素抵抗和2型糖尿病的发展。海洋来源的N-3多不饱和脂肪酸(PUFAs)在消退炎症和发挥有益的代谢作用方面发挥着重要作用。通过在小鼠和超重/肥胖的2型糖尿病患者身上的实验，我们阐明了补充n-3PUFA后血清和Wat中存在的羟基脂肪酸脂肪酸酯的新成员--二十二碳六烯酸(DHA)和亚油酸衍生的脂素的结构。这些化合物含有酯化为9-和13-羟基十八碳二烯酸(HLA)或14-羟基二十二碳六烯酸(HDHA)的DHA，称为9-DHAHL A、13-DHAHL A和14-DHAHDHA，由脂肪细胞合成，其浓度与WAT中DHA来源的保护素和解析素的浓度相当。13-DHAHLA具有抗炎和促溶解作用，同时可减少脂多糖对巨噬细胞的激活，增强酵母多糖颗粒的吞噬功能。我们的结果证明了新型脂质介质的存在，这些介质参与了n-3多不饱和脂肪酸在小鼠和人类中的有益抗炎作用。
White adipose tissue (WAT) is a complex organ with both metabolic and endocrine functions. Dysregulation of all of these functions of WAT, together with low-grade inflammation of the tissue in obese individuals, contributes to the development of insulin resistance and type 2 diabetes. n-3 polyunsaturated fatty acids (PUFAs) of marine origin play an important role in the resolution of inflammation and exert beneficial metabolic effects. Using experiments in mice and overweight/obese patients with type 2 diabetes, we elucidated the structures of novel members of fatty acid esters of hydroxy fatty acids-lipokines derived from docosahexaenoic acid (DHA) and linoleic acid, which were present in serum and WAT after n-3 PUFA supplementation. These compounds contained DHA esterified to 9- and 13-hydroxyoctadecadienoic acid (HLA) or 14-hydroxydocosahexaenoic acid (HDHA), termed 9-DHAHLA, 13-DHAHLA, and 14-DHAHDHA, and were synthesized by adipocytes at concentrations comparable to those of protectins and resolvins derived from DHA in WAT. 13-DHAHLA exerted anti-inflammatory and proresolving properties while reducing macrophage activation by lipopolysaccharides and enhancing the phagocytosis of zymosan particles. Our results document the existence of novel lipid mediators, which are involved in the beneficial anti-inflammatory effects attributed to n-3 PUFAs, in both mice and humans.