iScience (Apr 2024)
T cells with increased responsiveness cause obesity in mice without diet intervention
- 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
Affiliations
- Ida Gregersen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Xiang Y. Kong
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Sander Kooijman
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
- Håvard Foyn
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Department of Cancer Immunology, Institute of Cancer Research, Oslo University Hospital, 0424 Oslo, Norway
- Helene Grannes
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Maria B. Olsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Anna M. Lone
- Department of Cancer Immunology, Institute of Cancer Research, Oslo University Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, 0317 Oslo, Norway
- Kuan Yang
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Ana Quiles-Jiménez
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Marianne Tran
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Jonas Øgaard
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Filip M. Segers
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Azita Rashidi
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Ellen Lund Sagen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Knut H. Lauritzen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Amanda C.M. Pronk
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
- Jan Freark de Boer
- University Medical Center Groningen, Department of Pediatrics, Section Molecular Metabolism & Nutrition, Department of Laboratory Medicine, Groningen, the Netherlands
- Kirsten B. Holven
- Department of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, Norway
- Espen Melum
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammatory Diseases and Transplantation, Oslo University Hospital Rikshospitalet, Oslo, Norway; Hybrid Technology Hub-Centre of Excellence, Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
- Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway
- Kjetil Taskén
- Department of Cancer Immunology, Institute of Cancer Research, Oslo University Hospital, 0424 Oslo, Norway; K.G. Jebsen Centre for B Cell Malignancies, Institute of Clinical Medicine, University of Oslo, 0317 Oslo, Norway
- Sverre Holm
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway
- Patrick C.N. Rensen
- Department of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the Netherlands
- Tuva B. Dahl
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Department of Research and Development, Division of Emergencies and Critical Care, Oslo University Hospital HF, Rikshospitalet, Oslo, Norway
- Bente Halvorsen
- Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway; Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, USA; Corresponding author
- Journal volume & issue
-
Vol. 27,
no. 4
p. 109471
Abstract
Summary: 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.
