Developing a Mouse Model to Test the Impact of Metabolic Syndrome on Systemic Lupus Erythematosus‐Induced Organ Damage

Abstract

Background/hypothesis of the studyMetabolic syndrome (MetS) is characterized by a group of conditions that include obesity, impaired glucose tolerance, dyslipidemia and hypertension. MetS is common in systemic erythematosus (SLE) patients and associated with increased cardio‐renal risk. The present study was carried out to develop a model to use in future investigations of whether MetS accelerates SLE‐induced organ damage.Methods and ResultsFemale C57BL/6 mice were untreated or treated epicutaneously with the TLR7 agonist imiquimod (IMQ) and fed a high‐fat (HF) “Western” diet (fat 42% kcal, sucrose 34% kcal) or control diet (fat 12.6% kcal, sucrose 34% kcal) for 6 weeks. Data at 6 weeks were compared by two‐way ANOVA, with n=8 mice per group. Supporting early‐stage induction of autoimmunity, spleen weights were significantly increased in IMQ‐treated mice (PTreatment<0.001), and renal cortex IgG deposition was confirmed by western blot. Increased body weight, gonadal fat pad mass, and plasma leptin levels were observed between HF and control animals (PDiet<0.001) for both IMQ and untreated mice. At the 6th week, HF animals showed an inrease in 24‐hour calorie intake (PDiet<0.05) in contrast to control animals. At the same time, HF diet increased total cholesterol (PDiet<0.05) when compared with control diet‐fed animals. However, the increase in these parameters with HF diet was significantly diminished in IMQ‐treated mice (PDiet*Treatment<0.05). Both the HF diet (PDiet<0.001) and IMQ treatment (PTreatment<0.05) significantly increased fasting blood glucose. IMQ treatment affected fasting insulin concentrations in a diet‐dependent manner (PDiet*Treatment<0.01), with hyperinsulinemia observed in IMQ‐HF treated mice (178±8 μIU/ml) compared to IMQ‐treated control diet mice (49±8 μIU/ml; P<0.05 by Bonferroni post‐hoc test), with plasma insulin similar between untreated mice on HF (112±19 μIU/ml) and control diets (98±20 μIU/ml; P>0.05).ConclusionTogether, these data indicate that the IMQ model of SLE is associated with metabolic alterations, impaired glycemic control, hypercholesterolemia, and hyperinsulinemia under HF intake conditions. In the future, this model may be helpful to understand the complex relationship between MetS and organ damage in SLE.