Frontiers in Immunology (Jul 2019)
NLRP3 Inflammasome Promotes Myocardial Remodeling During Diet-Induced Obesity
- Marina Sokolova,
- Marina Sokolova,
- Marina Sokolova,
- Marina Sokolova,
- Ivar Sjaastad,
- Ivar Sjaastad,
- Mieke C. Louwe,
- Mieke C. Louwe,
- Mieke C. Louwe,
- Mieke C. Louwe,
- Katrine Alfsnes,
- Jan Magnus Aronsen,
- Jan Magnus Aronsen,
- Lili Zhang,
- Lili Zhang,
- Solveig B. Haugstad,
- Solveig B. Haugstad,
- Bård Andre Bendiksen,
- Bård Andre Bendiksen,
- Jonas Øgaard,
- Marte Bliksøen,
- Egil Lien,
- Egil Lien,
- Rolf K. Berge,
- Pål Aukrust,
- Pål Aukrust,
- Pål Aukrust,
- Pål Aukrust,
- Trine Ranheim,
- Trine Ranheim,
- Trine Ranheim,
- Trine Ranheim,
- Arne Yndestad,
- Arne Yndestad,
- Arne Yndestad,
- Arne Yndestad
Affiliations
- Marina Sokolova
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Marina Sokolova
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Marina Sokolova
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Marina Sokolova
- K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway
- Ivar Sjaastad
- K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway
- Ivar Sjaastad
- Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway
- Mieke C. Louwe
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Mieke C. Louwe
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Mieke C. Louwe
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Mieke C. Louwe
- K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway
- Katrine Alfsnes
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Jan Magnus Aronsen
- Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway
- Jan Magnus Aronsen
- Bjørknes College, Oslo, Norway
- Lili Zhang
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Lili Zhang
- Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway
- Solveig B. Haugstad
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Solveig B. Haugstad
- Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway
- Bård Andre Bendiksen
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Bård Andre Bendiksen
- Institute for Experimental Medical Research, Oslo University Hospital Ullevål, Oslo, Norway
- Jonas Øgaard
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Marte Bliksøen
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Egil Lien
- Division of Infectious Diseases and Immunology, University of Massachusetts Medical School, Worcester, MA, United States
- Egil Lien
- Centre of Molecular Inflammation Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Rolf K. Berge
- Department of Clinical Science, Department of Heart Disease, Haukeland University Hospital, University of Bergen, Bergen, Norway
- Pål Aukrust
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Pål Aukrust
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Pål Aukrust
- K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway
- Pål Aukrust
- 0Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
- Trine Ranheim
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Trine Ranheim
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Trine Ranheim
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Trine Ranheim
- K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway
- Arne Yndestad
- Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway
- Arne Yndestad
- Faculty of Medicine, Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Arne Yndestad
- Center for Heart Failure Research, University of Oslo, Oslo, Norway
- Arne Yndestad
- K.G. Jebsen Center for Cardiac Research, University of Oslo, Oslo, Norway
- DOI
- https://doi.org/10.3389/fimmu.2019.01621
- Journal volume & issue
-
Vol. 10
Abstract
Background: Obesity is an increasingly prevalent metabolic disorder in the modern world and is associated with structural and functional changes in the heart. The NLRP3 inflammasome is an innate immune sensor that can be activated in response to endogenous danger signals and triggers activation of interleukin (IL)-1β and IL-18. Increasing evidence points to the involvement of the NLRP3 inflammasome in obesity-induced inflammation and insulin resistance, and we hypothesized that it also could play a role in the development of obesity induced cardiac alterations.Methods and Results: WT, Nlrp3−/−, and ASC−/− (Pycard−/−) male mice were exposed to high fat diet (HFD; 60 cal% fat) or control diet for 52 weeks. Cardiac structure and function were evaluated by echocardiography and magnetic resonance imaging, respectively. Whereas, NLRP3 and ASC deficiency did not affect the cardiac hypertrophic response to obesity, it was preventive against left ventricle concentric remodeling and impairment of diastolic function. Furthermore, whereas NLRP3 and ASC deficiency attenuated systemic inflammation in HFD fed mice; long-term HFD did not induce significant cardiac fibrosis or inflammation, suggesting that the beneficial effects of NLRP3 inflammasome deficiency on myocardial remodeling at least partly reflect systemic mechanisms. Nlrp3 and ASC (Pycard) deficient mice were also protected against obesity-induced systemic metabolic dysregulation, as well as lipid accumulation and impaired insulin signaling in hepatic and cardiac tissues.Conclusions: Our data indicate that the NLRP3 inflammasome modulates cardiac concentric remodeling in obesity through effects on systemic inflammation and metabolic disturbances, with effect on insulin signaling as a potential mediator within the myocardium.
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