Gregersen Ida, Kong Xiang Y, Kooijman Sander, Foyn Håvard, Grannes Helene, Olsen Maria B, Lone Anna M, Yang Kuan, Quiles-Jiménez Ana, Tran Marianne, Øgaard Jonas, Segers Filip M, Rashidi Azita, Sagen Ellen Lund, Lauritzen Knut H, Pronk Amanda C M, de Boer Jan Freark, Holven Kirsten B, Melum Espen, Aukrust Pål, Taskén Kjetil, Holm Sverre, Rensen Patrick C N, Dahl Tuva B, Halvorsen Bente
Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway.
Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands.
iScience. 2024 Mar 11;27(4):109471. doi: 10.1016/j.isci.2024.109471. eCollection 2024 Apr 19.
Obesity is a complex multicausal disease that can cause morbidity and mortality, and there is need for improved knowledge on the underlying mechanisms. Using a mouse model of increased T cell responsiveness, we show that development of obesity can be driven by immune cells. This was confirmed with bone marrow transplantation and adoptive T cell transfer to several recipient mouse models. Single-cell RNA sequencing and CyTOF analysis showed that the mice display altered composition of circulating T cells and increased T cell activation in visceral adipose tissue, suggesting activated T cells as critical players in the increased fat mass. In this study, we provide evidence that obesity can be driven by immune cell activity and in particular by T cells, which could have broad implications for prevention and treatment of this condition.
肥胖是一种复杂的多病因疾病，可导致发病和死亡，因此需要增进对其潜在机制的了解。利用T细胞反应性增强的小鼠模型，我们发现肥胖的发展可能由免疫细胞驱动。这通过骨髓移植和将T细胞过继转移到多个受体小鼠模型得到了证实。单细胞RNA测序和质谱流式细胞分析表明，这些小鼠循环T细胞的组成发生改变，内脏脂肪组织中的T细胞活化增加，提示活化的T细胞是脂肪量增加的关键因素。在本研究中，我们提供证据表明肥胖可由免疫细胞活性驱动，特别是由T细胞驱动，这可能对该疾病的预防和治疗具有广泛意义。
