TY - JOUR T1 - Lupus pathogenesis and autoimmunity are exacerbated by high fat diet-induced obesity in MRL/lpr mice JF - Lupus Science & Medicine JO - Lupus Sci Med DO - 10.1136/lupus-2023-000898 VL - 10 IS - 1 SP - e000898 AU - Xin Zhang AU - Juan Meng AU - Xuhua Shi AU - Robert James Quinet AU - William Davis AU - Jerald Zakem AU - Chandana Keshavamurthy AU - Ronak Patel AU - Gitanjali Lobo AU - Linh Hellmers AU - Alicia Nicole Ray AU - Laura E Rivers AU - Hiba Ali AU - Therese Posas-Mendoza AU - Chad Hille AU - Zongbing You Y1 - 2023/04/01 UR - http://lupus.bmj.com/content/10/1/e000898.abstract N2 - Objective SLE is an autoimmune disease characterised by persistent inflammation and autoantibody production. Genetic predisposition and environmental factors such as a high-fat diet (HFD) may contribute to lupus development. However, the immune cell profile and gender difference in response to HFD in lupus have not been reported. Here we investigated the impact of HFD on lupus pathogenesis and autoimmunity using lupus-prone mice.Methods Thirty male and 30 female MRL/lymphoproliferation (lpr) mice were fed with regular diet (RD) or HFD. Body weights were recorded weekly. SLE progression was monitored by skin lesion, urine protein, titres of antidouble-strand DNA (dsDNA) and ANA. At week 14, kidney and skin tissue sections were stained with H&E and periodic acid–Schiff to detect histological kidney index and skin score. Splenocytes were identified by immunofluorescence staining and flow cytometry.Results HFD significantly increased body weight and lipid levels compared with RD (p<0.01). Skin lesions were observed in 55.6% of the HFD group compared with 11.1% of the RD group, with greater histopathological skin scores in the female HFD group (p<0.01). Although both male and female mice had higher serum IgG in the HFD group than in the RD group, only the male HFD group showed an increased trend in anti-dsDNA Ab and ANA titres. Kidney pathological changes in the HFD group were more severe in male mice than in female mice (p<0.05), detected by proteinuria, kidney index and glomerular cell proliferation. Significant increases of germinal centre B cells and T follicular helper cells were observed in the spleens of HFD mice (p<0.05).Conclusion HFD induced an accelerated and exacerbated lupus development and autoimmunity in MRL/lpr mice. Our results parallel many known clinical lupus phenotypes and sexual dimorphism in which male patients are likelier to have a severe disease (nephritis) than female lupus patients who may have a broader range of lupus symptoms.Data are available upon reasonable request. Data may be obtained from a third party and are not publicly available. All data relevant to the study are included in the article or uploaded as supplementary information. ER -