Ertunc Meric Erikci, Konduri Srihari, Ma Zhichen, Pinto Antonio F M, Donaldson Cynthia J, Momper Jeremiah, Siegel Dionicio, Saghatelian Alan
Clayton Foundation Laboratories for Peptide Biology, The Salk Institute for Biological Studies, La Jolla, California, USA.
The Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, California, USA.
J Biol Chem. 2024 Dec;300(12):107972. doi: 10.1016/j.jbc.2024.107972. Epub 2024 Nov 5.
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.
自从发现脂肪酸羟基脂肪酸（FAHFAs）以来，在了解其调控、生物化学和生理活性方面已取得重大进展。在此，我们通过揭示炎症在白色脂肪组织库以及与巨噬细胞共培养的脂肪细胞中诱导脂肪酸羟基硬脂酸和脂肪酸羟基十八碳二烯酸的产生，为这一认识做出贡献。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FAHFAs由于其低浓度不太可能具有抗炎作用，但将促炎羟基脂肪酸转化为FAHFAs可能会减轻炎症。事实上，我们证明促炎脂质，如羟基二十碳四烯酸（HETEs）和白三烯B4（LTB4），可被培养中的细胞转化为弱抗炎的FAHFAs。
