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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/231650
MRP8-Cre Transgenic Mice Are Resistant to Weight Gain and Diet-Induced Obesity Independently of Neutrophils
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Obesity is a major risk factor for metabolic syndrome, cancer, diabetes, and other diseases. The occurrence of comorbidities is associated with systemic and adipose tissue inflammation, which is marked by the presence of macrophages and neutrophils in adipose tissue. The role of neutrophils in driving adipose tissue inflammation and pathology is understudied and may hold therapeutic promise. MRP8Cre transgenic mice are frequently used to investigate neutrophil functions. A recent report demonstrates that the insertion of the MRP8Cre transgene resulted in whole-body deletion of Ap1s1 and Serpine1, the latter encoding the pro-obesogenic factor plasminogen activator inhibitor-1 (PAI-1). Here, we show that MRP8Cre transgenic mice have lower body weight than their littermate controls on a standard chow diet. Furthermore, they are resistant to weight gain, adipose tissue hypertrophy, systemic deregulation of glucose metabolism, infiltration of macrophages into AT, and liver steatosis upon feeding of obesogenic, high-fat diets (HFD). Mechanistically, this was independent of neutrophils or bone marrow-derived cells, sex, age of the mice, the duration of the HFD feeding, treatment start, housing facility, or the original source of the mice. The expression of Sepine1/PAI-1 and Ap1s1 is globally reduced across metabolic organs of MRP8Cre mice irrespective of diet, thus phenocopying previous reports of the obesity-protective effect of PAI-1 depletion in mice. Our findings demonstrate the limited applicability of MRP8Cre mice for obesity or metabolic studies due to the observed off-target effects and highlight the need for respective controls when using transgenic mice, such as Cre-only controls or use of independent Cre lines for studies involving the Cre/loxP system.
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European Journal of Immunology, Volume56, Issue9 September 2026 e70271
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FORISCH, Stephan, et al. MRP8-Cre Transgenic Mice Are Resistant to Weight Gain and Diet-Induced Obesity Independently of Neutrophils. 2026. 56. Vol. 9. [consulted: 28 of September of 2026]. Available at: https://hdl.handle.net/2445/231650