Since the discovery of fatty acid hydroxy fatty acids (FAHFAs), significant progress has been made in understanding their regulation, biochemistry, and physiological activities. Here, we contribute to this understanding by revealing that inflammation induces the production of fatty acid hydroxy stearic acids and fatty acid hydroxyoctadecadienoic acids in white adipose tissue depots and in adipocytes cocultured with macrophages. In lipopolysaccharide (LPS)-induced coculture systems, we confirm that adipose triglyceride lipase is required for inflammation-induced FAHFA generation and demonstrate that inflammation is necessary for producing hydroxy fatty acids. Chemically synthesized fatty acid hydroxyoctadecadienoic acids show anti-inflammatory activities in vivo, but only at supraphysiological concentrations. While endogenous FAHFAs are unlikely to be anti-inflammatory due to their low concentrations, conversion of proinflammatory hydroxy fatty acids into FAHFAs may dampen inflammation. Indeed, we demonstrate that proinflammatory lipids, such as hydroxyeicosatetraenoic acids (HETEs) and leukotriene B4 (LTB4), can be converted by cells in culture to weakly anti-inflammatory FAHFAs.

中文翻译：

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急性炎症上调脂肪组织和分化脂肪细胞中的 FAHFA


自从脂肪酸羟基脂肪酸 （FAHFA） 被发现以来，在了解它们的调节、生物化学和生理活性方面取得了重大进展。在这里，我们通过揭示炎症诱导白色脂肪组织库和与巨噬细胞共培养的脂肪细胞中脂肪酸羟基硬脂酸和脂肪酸羟基十八碳二烯酸的产生来促进这种理解。在脂多糖 （LPS） 诱导的共培养系统中，我们证实脂肪甘油三酯脂肪酶是炎症诱导的 FAHFA 生成所必需的，并证明炎症是产生羟基脂肪酸所必需的。化学合成的脂肪酸羟基十八碳二烯酸在 体内显示出抗炎活性，但仅在超生理浓度下。虽然内源性 FAHFA 由于浓度低而不太可能具有抗炎作用，但促炎羟基脂肪酸转化为 FAHFA 可能会抑制炎症。事实上，我们证明促炎脂质，如羟基二十碳四烯酸 （HETE） 和白三烯 B4 （LTB4），可以被培养中的细胞转化为弱抗炎 FAHFA。