MRP8-Cre transgenic mice are protected from weight gain, diet-induced obesity and related pathologies independently of neutrophils

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 are 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 highlights 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.