Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures.
Lipoxins reduce obesity-induced adipose tissue inflammation in 3D-cultured human adipocytes and explant cultures.
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DOI：
10.1016/j.isci.2022.104602
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发表时间：
2022-07-15
期刊：
影响因子：
5.8
通讯作者：
Borgeson, Emma
中科院分区：
文献类型：
--
作者：
Sotak, Matus;Rajan, Meenu Rohini;Clark, Madison;Harms, Matthew;Rani, Alankrita;Kraft, Jamie D.;Tandio, David;Shen, Tong;Borkowski, Kamil;Fiehn, Oliver;Newman, John W.;Quiding-Jarbrink, Marianne;Biorserud, Christina;Apelgren, Peter;Staalesen, Trude;Hagberg, Carolina E.;Boucher, Jeremie;Wallenius, Ville;Lange, Stephan;Borgeson, Emma
脂肪组织炎症驱动肥胖相关的心脏代谢疾病。通过给予脂氧素A4（一种专门的促分解脂质介质）来增强内源性分解机制，已显示可减少脂肪炎症并随后保护小鼠免受肥胖诱导的全身性疾病。在这里，我们证明了脂氧素可以减少3D培养的人脂肪细胞和肥胖患者脂肪组织外植体的炎症。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好。有反应的患者的特征是C反应蛋白的全身水平升高，这会导致培养的人脂肪细胞发生炎症。应答者似乎更倾向于产生抗炎氧脂素，并显示前列腺素D2水平升高，这与脂氧素生成酶的转录相关。使用外植体培养，这项研究提供了第一个概念验证证据，支持脂氧素在减少人类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量身定制的个性化药物方法。3D细胞培养系统放大人脂肪细胞中脂氧素介导的反应脂氧素减少人脂肪组织外植体中与肥胖相关的炎症脂氧素介导的反应的幅度与患者的血浆CRP水平相关脂氧素反应者改变了炎症和脂肪组织脂质分布精密医学;生物科学;生理学;人体代谢;细胞生物学
Adipose tissue inflammation drives obesity-related cardiometabolic diseases. Enhancing endogenous resolution mechanisms through administration of lipoxin A4, 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. 3D cell culture systems amplify lipoxin-mediated responses in human adipocytes Lipoxins reduce obesity-related inflammation in human adipose tissue explants The amplitude of a lipoxin-mediated response correlates with a patient’s plasma CRP level Lipoxin responders have altered inflammatory and adipose tissue lipid profiles Precision medicine; Biological sciences; Physiology; Human metabolism; Cell biology
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DOI：
10.1161/atvbaha.115.305289
发表时间：
2015-10
期刊：
Arteriosclerosis, thrombosis, and vascular biology
影响因子：
--
作者：
Durda P;Sabourin J;Lange EM;Nalls MA;Mychaleckyj JC;Jenny NS;Li J;Walston J;Harris TB;Psaty BM;Valdar W;Liu Y;Cushman M;Reiner AP;Tracy RP;Lange LA
通讯作者：
Lange LA
影响因子：
2.8
作者：
Graziani, Francesca;Biasucci, Luigi M.;Crea, Filippo
通讯作者：
Crea, Filippo
影响因子：
1.2
作者：
Alexandersson, Ida;Harms, Matthew J.;Boucher, Jeremie
通讯作者：
Boucher, Jeremie
影响因子：
5.5
作者：
Ioannidou, Anna;Alatar, Shemim;Hagberg, Carolina E.
通讯作者：
Hagberg, Carolina E.
DOI：
10.1016/j.plefa.2018.05.001
发表时间：
2018-07
期刊：
Prostaglandins, leukotrienes, and essential fatty acids
影响因子：
--
作者：
Agrawal K;Hassoun LA;Foolad N;Borkowski K;Pedersen TL;Sivamani RK;Newman JW
通讯作者：
Newman JW