T cells with increased responsiveness cause obesity in mice without diet intervention
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 confirm...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-04-01
|
| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224006928 |
| _version_ | 1797247734220062720 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Ida Gregersen |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-24T20:03:24Z |
| format | Article |
| id | doaj.art-4eebcfac72e641d6a1735c3f7f6c06bf |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-04-24T20:03:24Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-4eebcfac72e641d6a1735c3f7f6c06bf2024-03-24T07:00:03ZengElsevieriScience2589-00422024-04-01274109471T cells with increased responsiveness cause obesity in mice without diet interventionIda Gregersen0Xiang Y. Kong1Sander Kooijman2Håvard Foyn3Helene Grannes4Maria B. Olsen5Anna M. Lone6Kuan Yang7Ana Quiles-Jiménez8Marianne Tran9Jonas Øgaard10Filip M. Segers11Azita Rashidi12Ellen Lund Sagen13Knut H. Lauritzen14Amanda C.M. Pronk15Jan Freark de Boer16Kirsten B. Holven17Espen Melum18Pål Aukrust19Kjetil Taskén20Sverre Holm21Patrick C.N. Rensen22Tuva B. Dahl23Bente Halvorsen24Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsResearch 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, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment 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, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsUniversity Medical Center Groningen, Department of Pediatrics, Section Molecular Metabolism & Nutrition, Department of Laboratory Medicine, Groningen, the NetherlandsDepartment of Nutrition, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway; Norwegian National Advisory Unit on Familial Hypercholesterolemia, Oslo University Hospital, Oslo, NorwayResearch 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, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, Norway; Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayDepartment 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, NorwayResearch Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Sognsvannsveien 20, 0372 Oslo, NorwayDepartment of Medicine, Division of Endocrinology, Leiden University Medical Center, Leiden, the Netherlands; Einthoven Laboratory for Experimental Vascular Medicine, Leiden University Medical Center, Leiden, the NetherlandsResearch 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, NorwayResearch 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224006928ImmunologyNutrition |
| spellingShingle | 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 T cells with increased responsiveness cause obesity in mice without diet intervention iScience Immunology Nutrition |
| title | T cells with increased responsiveness cause obesity in mice without diet intervention |
| title_full | T cells with increased responsiveness cause obesity in mice without diet intervention |
| title_fullStr | T cells with increased responsiveness cause obesity in mice without diet intervention |
| title_full_unstemmed | T cells with increased responsiveness cause obesity in mice without diet intervention |
| title_short | T cells with increased responsiveness cause obesity in mice without diet intervention |
| title_sort | t cells with increased responsiveness cause obesity in mice without diet intervention |
| topic | Immunology Nutrition |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224006928 |
| work_keys_str_mv | AT idagregersen tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT xiangykong tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT sanderkooijman tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT havardfoyn tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT helenegrannes tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT mariabolsen tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT annamlone tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT kuanyang tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT anaquilesjimenez tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT mariannetran tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT jonasøgaard tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT filipmsegers tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT azitarashidi tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT ellenlundsagen tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT knuthlauritzen tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT amandacmpronk tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT janfrearkdeboer tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT kirstenbholven tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT espenmelum tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT palaukrust tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT kjetiltasken tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT sverreholm tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT patrickcnrensen tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT tuvabdahl tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention AT bentehalvorsen tcellswithincreasedresponsivenesscauseobesityinmicewithoutdietintervention |