Soták Matúš, Rajan Meenu Rohini, Clark Madison, Harms Matthew, Rani Alankrita, Kraft Jamie D, Tandio David, Shen Tong, Borkowski Kamil, Fiehn Oliver, Newman John W, Quiding-Järbrink Marianne, Biörserud Christina, Apelgren Peter, Staalesen Trude, Hagberg Carolina E, Boucher Jeremie, Wallenius Ville, Lange Stephan, Börgeson Emma
Department of Molecular and Clinical Medicine, Wallenberg Laboratory, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 40530 Gothenburg, Sweden.
Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, 40530 Gothenburg, Sweden.
iScience. 2022 Jun 11;25(7):104602. doi: 10.1016/j.isci.2022.104602. eCollection 2022 Jul 15.
Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A, a specialized pro-resolving lipid mediator, was shown to reduce adipose inflammation and subsequently protects against obesity-induced systemic disease in mice. Here, we demonstrate that lipoxins reduce inflammation in 3D-cultured human adipocytes and adipose tissue explants from obese patients. Approximately 50% of patients responded particularly well to lipoxins by reducing inflammatory cytokines and promoting an anti-inflammatory M2 macrophage phenotype. Responding patients were characterized by elevated systemic levels of C-reactive protein, which causes inflammation in cultured human adipocytes. Responders appeared more prone to producing anti-inflammatory oxylipins and displayed elevated prostaglandin D2 levels, which has been interlinked with transcription of lipoxin-generating enzymes. Using explant cultures, this study provides the first proof-of-concept evidence supporting the therapeutic potential of lipoxins in reducing human adipose tissue inflammation. Our data further indicate that lipoxin treatment may require a tailored personalized-medicine approach.
脂肪组织炎症会引发与肥胖相关的心脏代谢疾病。通过给予脂氧素A（一种特殊的促消退脂质介质）来增强内源性消退机制，已被证明可减轻脂肪炎症，并随后预防小鼠肥胖诱导的全身性疾病。在此，我们证明脂氧素可减轻肥胖患者三维培养的人脂肪细胞和脂肪组织外植体中的炎症。大约50%的患者通过减少炎性细胞因子和促进抗炎M2巨噬细胞表型，对脂氧素反应特别良好。有反应的患者的特征是全身C反应蛋白水平升高，C反应蛋白会在培养的人脂肪细胞中引发炎症。有反应者似乎更易于产生抗炎氧化脂质，并表现出前列腺素D2水平升高，前列腺素D2已与脂氧素生成酶的转录相关联。利用外植体培养，本研究提供了首个概念验证证据，支持脂氧素在减轻人脂肪组织炎症方面的治疗潜力。我们的数据进一步表明，脂氧素治疗可能需要采用个性化医疗方法。
