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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