Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice
Abstract Background The Stimulator of Interferon Genes (STING) pathway is pivotal in innate immunity, facilitating the detection of cytosolic DNA and initiating type I interferon-dependent responses. In addition to its immunological roles, STING has been increasingly associated with metabolic regula...
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BMC
2025-07-01
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| Online Access: | https://doi.org/10.1186/s40659-025-00624-3 |
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| author | Ian Riquelme Daniela Carrillanca Camila Sánchez-Pérez Andrea Monterroza Bairon Hernández-Rojas Gonzalo Riadi Gonzalo I. Cancino Paola Murgas |
| author_facet | Ian Riquelme Daniela Carrillanca Camila Sánchez-Pérez Andrea Monterroza Bairon Hernández-Rojas Gonzalo Riadi Gonzalo I. Cancino Paola Murgas |
| author_sort | Ian Riquelme |
| collection | DOAJ |
| description | Abstract Background The Stimulator of Interferon Genes (STING) pathway is pivotal in innate immunity, facilitating the detection of cytosolic DNA and initiating type I interferon-dependent responses. In addition to its immunological roles, STING has been increasingly associated with metabolic regulation, since research indicates that its inhibition can diminish inflammation, lipid accumulation, and tissue damage in obesity and other metabolic disorders. The findings have prompted the suggestion of STING inhibition as a viable treatment approach for metabolic illness. Nonetheless, the physiological function of STING in lipid homeostasis under normal settings remains largely unexplored, as does the impact of its absence on metabolism throughout various life stages in the absence of disease. This information deficit is crucial, particularly in light of the increasing interest in the long-term pharmacological suppression of STING. Results To examine the function of STING in lipid metabolism during physiological, non-pathological conditions throughout the lifespan, we assessed WT and STINGKO mice at various ages and discovered that STING deficiency results in a consistent increase in body weight, independent of alterations in locomotor activity or food consumption. STINGKO mice exhibited markedly increased circulation levels of triglycerides and total cholesterol. Histological and morphological analysis demonstrated augmented fat accumulation in adipose and hepatic tissues, despite the lack of nutritional or genetic metabolic stress. These findings indicate a crucial function for STING in the control of lipid homeostasis across the lifespan. Conclusions In contrast to earlier research conducted under pathological conditions, our findings indicate that the total absence of STING expression in healthy contexts leads to heightened lipid accumulation in tissues and blood. These findings underscore an unforeseen function of STING as a modulator of lipid metabolism in the context of longevity. They caution against the prolonged use of STING inhibitors, as chronic STING suppression may lead to detrimental metabolic effects. This study offers new insights into the non-immune roles of STING, indicating its significance in preserving metabolic equilibrium throughout the lifetime. |
| format | Article |
| id | doaj-art-3ea3d145d3de45b684aef3d2a693ae96 |
| institution | DOAJ |
| issn | 0717-6287 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj-art-3ea3d145d3de45b684aef3d2a693ae962025-08-20T03:03:34ZengBMCBiological Research0717-62872025-07-0158111710.1186/s40659-025-00624-3Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in miceIan Riquelme0Daniela Carrillanca1Camila Sánchez-Pérez2Andrea Monterroza3Bairon Hernández-Rojas4Gonzalo Riadi5Gonzalo I. Cancino6Paola Murgas7Escuela de Medicina, Facultad de Medicina y Ciencia, Universidad San SebastiánEscuela de Medicina, Facultad de Medicina y Ciencia, Universidad San SebastiánEscuela de Medicina, Facultad de Medicina y Ciencia, Universidad San SebastiánFacultad de Medicina, Instituto de Inmunología y Parasitología, Universidad Austral de Chile Program in Sciences Mention Modeling of Chemical and Biological Systems, School of Bioinformatics Engineering, Center for Bioinformatics, Simulation and Modeling, CBSM, Department of Bioinformatics, Faculty of Engineering, University of TalcaCenter for Bioinformatics, Simulation and Modeling, CBSM, Department of Bioinformatics, Faculty of Engineering, University of TalcaLaboratorio de Neurobiología, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de ChileEscuela de Medicina, Facultad de Medicina y Ciencia, Universidad San SebastiánAbstract Background The Stimulator of Interferon Genes (STING) pathway is pivotal in innate immunity, facilitating the detection of cytosolic DNA and initiating type I interferon-dependent responses. In addition to its immunological roles, STING has been increasingly associated with metabolic regulation, since research indicates that its inhibition can diminish inflammation, lipid accumulation, and tissue damage in obesity and other metabolic disorders. The findings have prompted the suggestion of STING inhibition as a viable treatment approach for metabolic illness. Nonetheless, the physiological function of STING in lipid homeostasis under normal settings remains largely unexplored, as does the impact of its absence on metabolism throughout various life stages in the absence of disease. This information deficit is crucial, particularly in light of the increasing interest in the long-term pharmacological suppression of STING. Results To examine the function of STING in lipid metabolism during physiological, non-pathological conditions throughout the lifespan, we assessed WT and STINGKO mice at various ages and discovered that STING deficiency results in a consistent increase in body weight, independent of alterations in locomotor activity or food consumption. STINGKO mice exhibited markedly increased circulation levels of triglycerides and total cholesterol. Histological and morphological analysis demonstrated augmented fat accumulation in adipose and hepatic tissues, despite the lack of nutritional or genetic metabolic stress. These findings indicate a crucial function for STING in the control of lipid homeostasis across the lifespan. Conclusions In contrast to earlier research conducted under pathological conditions, our findings indicate that the total absence of STING expression in healthy contexts leads to heightened lipid accumulation in tissues and blood. These findings underscore an unforeseen function of STING as a modulator of lipid metabolism in the context of longevity. They caution against the prolonged use of STING inhibitors, as chronic STING suppression may lead to detrimental metabolic effects. This study offers new insights into the non-immune roles of STING, indicating its significance in preserving metabolic equilibrium throughout the lifetime.https://doi.org/10.1186/s40659-025-00624-3STINGLipid metabolismTriglyceridesCholesterolAgingAdipose tissue |
| spellingShingle | Ian Riquelme Daniela Carrillanca Camila Sánchez-Pérez Andrea Monterroza Bairon Hernández-Rojas Gonzalo Riadi Gonzalo I. Cancino Paola Murgas Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice Biological Research STING Lipid metabolism Triglycerides Cholesterol Aging Adipose tissue |
| title | Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice |
| title_full | Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice |
| title_fullStr | Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice |
| title_full_unstemmed | Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice |
| title_short | Loss of stimulator of interferon genes (STING) promotes accumulation of cholesterol and triglycerides throughout life in mice |
| title_sort | loss of stimulator of interferon genes sting promotes accumulation of cholesterol and triglycerides throughout life in mice |
| topic | STING Lipid metabolism Triglycerides Cholesterol Aging Adipose tissue |
| url | https://doi.org/10.1186/s40659-025-00624-3 |
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