Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes
Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cardiovascular risk (CV) factor. Interleukin-1β (IL-1β), a cytokine involved in the pathogenesis of obesity-associated inflammation and type 2 diabetes (T2D), promotes hepatic steatosis. The Canakinumab A...
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BMC
2025-06-01
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| Series: | Cardiovascular Diabetology |
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| Online Access: | https://doi.org/10.1186/s12933-025-02706-8 |
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| author | Paola Giustina Simeone Sarah Costantino Rossella Liani Romina Tripaldi Augusto Di Castelnuovo Armando Tartaro Alessandro Mengozzi Francesco Cosentino Francesco Cipollone Agostino Consoli Francesco Paneni Francesca Santilli |
| author_facet | Paola Giustina Simeone Sarah Costantino Rossella Liani Romina Tripaldi Augusto Di Castelnuovo Armando Tartaro Alessandro Mengozzi Francesco Cosentino Francesco Cipollone Agostino Consoli Francesco Paneni Francesca Santilli |
| author_sort | Paola Giustina Simeone |
| collection | DOAJ |
| description | Abstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cardiovascular risk (CV) factor. Interleukin-1β (IL-1β), a cytokine involved in the pathogenesis of obesity-associated inflammation and type 2 diabetes (T2D), promotes hepatic steatosis. The Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOS) trial showed that the inhibition of the IL-1β pathway was associated with a reduction of CV events in high-risk patients. The present study was designed to determine: (i) whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on MASLD extent and IL-1β expression in peripheral blood mononuclear cells from obese subjects with prediabetes or early T2D; (ii) whether baseline IL-1β levels may predict the extent of weight loss and related metabolic changes. Methods Thirty-two obese subjects with prediabetes (n = 16) or newly diagnosed T2D (n = 16), were randomized to the glucagon-like peptide receptor agonist (GLP1-RA) liraglutide or lifestyle counselling until achieving a comparable weight loss. Visceral adipose tissue (VAT) and gene expression of IL-1β in peripheral blood mononuclear cells were assessed by magnetic resonance and real time PCR, respectively. Results At baseline, IL-1β was positively correlated to body mass index (BMI), fasting plasma glucose, HbA1c, VAT, MASLD extent, platelet count, chemerin and interleukin-1 receptor antagonist (IL1-RA). After achievement of the weight loss target in the two groups, a significant but comparable reduction of IL-1β (p for difference = 0.56) was observed in both arms, in parallel with a comparable improvement in glycaemic control, C reactive protein (CRP), BMI and MASLD. Furthermore, basal IL-1β levels independently predicted the extent of MASLD decrease (p = 0.030); subjects in the highest tertile showed a median decrease of − 8.0 (95% CI − 12.3 to − 4.8) compared with − 23.0 (95% CI − 39.5 to − 16.3) in the lowest tertile. Conclusion In patients with obesity with initial impairment of glucose metabolism successful weight loss is associated with a reduction of both IL-1β levels and MASLD degree. Of interest, basal levels of IL-1β predict the extent of MASLD improvement, regardless of the intervention. Our results may set the stage for ad-hoc studies investigating the usefulness of baseline IL-1β a level as a drug-response biomarker. Graphical abstract |
| format | Article |
| id | doaj-art-4d63626c42ff4e428e840234a8b9e47e |
| institution | DOAJ |
| issn | 1475-2840 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
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| series | Cardiovascular Diabetology |
| spelling | doaj-art-4d63626c42ff4e428e840234a8b9e47e2025-08-20T02:39:44ZengBMCCardiovascular Diabetology1475-28402025-06-0124111510.1186/s12933-025-02706-8Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetesPaola Giustina Simeone0Sarah Costantino1Rossella Liani2Romina Tripaldi3Augusto Di Castelnuovo4Armando Tartaro5Alessandro Mengozzi6Francesco Cosentino7Francesco Cipollone8Agostino Consoli9Francesco Paneni10Francesca Santilli11Department of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-PescaraCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of ZurichDepartment of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-PescaraDepartment of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-PescaraResearch Unit of Epidemiology and Prevention, IRCCS NEUROMEDDepartment of Neuroscience & Imaging, University of ChietiCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of ZurichCardiology Unit, Department of Medicine, Solna, Karolinska Institutet, Karolinska University HospitalDepartment of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-PescaraDepartment of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-PescaraCenter for Translational and Experimental Cardiology (CTEC), Department of Cardiology, University Hospital Zurich, University of ZurichDepartment of Medicine and Aging Sciences, Center for Advanced Studies and Technology (CAST), University “G. d’Annunzio” of Chieti-PescaraAbstract Background Metabolic dysfunction-associated steatotic liver disease (MASLD) is a major cardiovascular risk (CV) factor. Interleukin-1β (IL-1β), a cytokine involved in the pathogenesis of obesity-associated inflammation and type 2 diabetes (T2D), promotes hepatic steatosis. The Canakinumab Anti-inflammatory Thrombosis Outcome (CANTOS) trial showed that the inhibition of the IL-1β pathway was associated with a reduction of CV events in high-risk patients. The present study was designed to determine: (i) whether an equal degree of weight loss by liraglutide or lifestyle changes has a different impact on MASLD extent and IL-1β expression in peripheral blood mononuclear cells from obese subjects with prediabetes or early T2D; (ii) whether baseline IL-1β levels may predict the extent of weight loss and related metabolic changes. Methods Thirty-two obese subjects with prediabetes (n = 16) or newly diagnosed T2D (n = 16), were randomized to the glucagon-like peptide receptor agonist (GLP1-RA) liraglutide or lifestyle counselling until achieving a comparable weight loss. Visceral adipose tissue (VAT) and gene expression of IL-1β in peripheral blood mononuclear cells were assessed by magnetic resonance and real time PCR, respectively. Results At baseline, IL-1β was positively correlated to body mass index (BMI), fasting plasma glucose, HbA1c, VAT, MASLD extent, platelet count, chemerin and interleukin-1 receptor antagonist (IL1-RA). After achievement of the weight loss target in the two groups, a significant but comparable reduction of IL-1β (p for difference = 0.56) was observed in both arms, in parallel with a comparable improvement in glycaemic control, C reactive protein (CRP), BMI and MASLD. Furthermore, basal IL-1β levels independently predicted the extent of MASLD decrease (p = 0.030); subjects in the highest tertile showed a median decrease of − 8.0 (95% CI − 12.3 to − 4.8) compared with − 23.0 (95% CI − 39.5 to − 16.3) in the lowest tertile. Conclusion In patients with obesity with initial impairment of glucose metabolism successful weight loss is associated with a reduction of both IL-1β levels and MASLD degree. Of interest, basal levels of IL-1β predict the extent of MASLD improvement, regardless of the intervention. Our results may set the stage for ad-hoc studies investigating the usefulness of baseline IL-1β a level as a drug-response biomarker. Graphical abstracthttps://doi.org/10.1186/s12933-025-02706-8Interleukin-1βObesityMASLDLiver diseasePrediabetesType 2 diabetes |
| spellingShingle | Paola Giustina Simeone Sarah Costantino Rossella Liani Romina Tripaldi Augusto Di Castelnuovo Armando Tartaro Alessandro Mengozzi Francesco Cosentino Francesco Cipollone Agostino Consoli Francesco Paneni Francesca Santilli Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes Cardiovascular Diabetology Interleukin-1β Obesity MASLD Liver disease Prediabetes Type 2 diabetes |
| title | Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes |
| title_full | Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes |
| title_fullStr | Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes |
| title_full_unstemmed | Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes |
| title_short | Interleukin-1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes |
| title_sort | interleukin 1β in circulating mononuclear cells predicts steatotic liver disease improvement after weight loss in subjects with obesity and prediabetes or type 2 diabetes |
| topic | Interleukin-1β Obesity MASLD Liver disease Prediabetes Type 2 diabetes |
| url | https://doi.org/10.1186/s12933-025-02706-8 |
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