T cells with increased responsiveness cause obesity in mice without diet intervention

T细胞反应性增强会导致小鼠肥胖,而无需饮食干预。

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作者:Ida Gregersen ,Xiang Y Kong ,Sander Kooijman ,Håvard Foyn ,Helene Grannes ,Maria B Olsen ,Anna M Lone ,Kuan Yang ,Ana Quiles-Jiménez ,Marianne Tran ,Jonas Øgaard ,Filip M Segers ,Azita Rashidi ,Ellen Lund Sagen ,Knut H Lauritzen ,Amanda C M Pronk ,Jan Freark de Boer ,Kirsten B Holven ,Espen Melum ,Pål Aukrust ,Kjetil Taskén ,Sverre Holm ,Patrick C N Rensen ,Tuva B Dahl ,Bente Halvorsen

Abstract

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.

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