Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice.
Multiomics reveals persistence of obesity-associated immune cell phenotypes in adipose tissue during weight loss and weight regain in mice.
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多组学研究揭示在小鼠体重减轻和体重恢复过程中，脂肪组织中与肥胖相关的免疫细胞表型持续存在。
DOI：
10.1038/s41467-022-30646-4
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发表时间：
2022-05-26
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
在脂肪组织内，免疫细胞和实质细胞紧密地相互作用，形成复杂的微环境。在肥胖症中，免疫细胞来源的炎症导致胰岛素抵抗和葡萄糖耐量减低。饮食诱导的体重减轻改善了糖耐量；然而，体重回升进一步加剧了肥胖所观察到的血糖稳态的损害。为了研究AT在小鼠体重减轻和体重恢复期间发生的免疫代谢适应，我们在雄性小鼠中使用了转录和表位的细胞索引(CITEseq)。肥胖诱导的AT免疫细胞印迹在体重下降过程中持续存在，并随着体重的恢复而逐渐恶化，最终导致体重循环小鼠中2型调节细胞的受损恢复、抗原提呈细胞的激活、T细胞的耗竭和巨噬细胞中脂质处理的增强。这项工作为理解体重循环加速代谢性疾病的免疫学原因提供了关键的基础。为了进一步发现，我们提供了一个开放访问的饮食诱导AT免疫细胞印记的门户网站：https://hastylab.shinyapps.io/MAIseq.脂肪免疫细胞与肥胖相关疾病有关，但对体重循环知之甚少。在这里，作者表明，减肥降低了糖尿病的风险，但炎性脂肪免疫细胞群持续存在，并可能在体重恢复后导致糖尿病风险恶化。
Within adipose tissue (AT), immune cells and parenchymal cells closely interact creating a complex microenvironment. In obesity, immune cell derived inflammation contributes to insulin resistance and glucose intolerance. Diet-induced weight loss improves glucose tolerance; however, weight regain further exacerbates the impairment in glucose homeostasis observed with obesity. To interrogate the immunometabolic adaptations that occur in AT during murine weight loss and weight regain, we utilized cellular indexing of transcriptomes and epitopes by sequencing (CITEseq) in male mice. Obesity-induced imprinting of AT immune cells persisted through weight-loss and progressively worsened with weight regain, ultimately leading to impaired recovery of type 2 regulatory cells, activation of antigen presenting cells, T cell exhaustion, and enhanced lipid handling in macrophages in weight cycled mice. This work provides critical groundwork for understanding the immunological causes of weight cycling-accelerated metabolic disease. For further discovery, we provide an open-access web portal of diet-induced AT immune cell imprinting: https://hastylab.shinyapps.io/MAIseq. Adipose immune cells contribute to obesity-related disease, but less is known about weight cycling. Here, authors show that weight loss reduces diabetes risk, but inflammatory adipose immune cell populations persist and may contribute to worsened diabetes risk upon weight regain.
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影响因子：
3.7
作者：
Barbosa-da-Silva S;Fraulob-Aquino JC;Lopes JR;Mandarim-de-Lacerda CA;Aguila MB
通讯作者：
Aguila MB
影响因子：
6
作者：
Biagi CAO Jr;Cury SS;Alves CP;Rabhi N;Silva WA Jr;Farmer SR;Carvalho RF;Batista ML Jr
通讯作者：
Batista ML Jr
影响因子：
7.7
作者：
Braune, Julia;Lindhorst, Andreas;Gericke, Martin
通讯作者：
Gericke, Martin
影响因子：
158.5
作者：
Bangalore, Sripal;Fayyad, Rana;Waters, David D.
通讯作者：
Waters, David D.
影响因子：
46.9
作者：
Dann, Emma;Henderson, Neil C.;Marioni, John C.
通讯作者：
Marioni, John C.