MRP8‐Cre Transgenic Mice Are Resistant to Weight Gain and Diet‐Induced Obesity Independently of Neutrophils

Year: 2026

Type: article

Abstract: ABSTRACT 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. MRP8 Cre transgenic mice are frequently used to investigate neutrophil functions. A recent report demonstrates that the insertion of the MRP8 Cre 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 MRP8 Cre 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 MRP8 Cre 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 MRP8 Cre 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.

Source: European Journal of Immunology

DOI: 10.1002/eji.70271

Authors: Stephan Forisch, Fatemeh Soltani, Laia Salvat Costa, Beatriz M. Cardoso, Yaiza Moreno Galiano, Cedric Duval, Robert A. S. Ariëns, Navdeep S. Chandel, Mari T. Kaartinen, Stefanie K. Wculek

Institutions: Institute for Research in Biomedicine, Barcelona Institute of Science and Technology, Universitat de Barcelona, McGill University, University of Leeds, Northwestern University

Language: English

Topic: Adipokines, Inflammation, and Metabolic Diseases

Subfield: Epidemiology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $4,550

Funders: Institute for Research in Biomedicine, McGill University, “la Caixa” Foundation, Ministerio de Ciencia, Innovación y Universidades, Centres de Recerca de Catalunya, European Commission, Generalitat de Catalunya, Ministerio de Ciencia e Innovación, Universitat de Barcelona, HORIZON EUROPE Framework Programme, Canadian Institutes of Health Research, European Research Council, Agencia Estatal de Investigación, Faculty of Medicine and Health, University of Sydney

OpenAlex ID: W7213245588