Lupus Pathogenesis And Autoimmunity Are Exacerbated By High Fat Diet-Induced Obesity In Mice

Abstract Objectives System lupus erythematosus (SLE)patients have increased prevalence of metabolic syndrome. Our previous data showed that circulating Tfh (Tfh) cells were increased in SLE patients and correlated to their disease activities. Here, we investigated the pathophysiologic link between fat-diet induced obesity and SLE and underlying mechanism using MRL/lpr lupus prone mice. Methods Twenty MRL/lpr mice were fed with a regular diet (RD) or high fat diet (HFD, 60% calories comprised of fat). Body weight and skin lesion were recorded weekly. Urine protein using Bradford assay was assessed. Blood was collected for IgG, anti-dsDNA and anti-nuclear antibody (ANA) detection. At the end of experiment of week 14, kidney and skin biopsy were embedded in paraffin for H&E, PAS, and Masson’s staining to detect lupus histopathological lesions and quantified as kidney index based on fibrinoid necrosis, periglomerular infiltrate, and inflammatory dermatitis. Spleen paraffin specimens were stained for Tfh cells markers. Results Obesity was achieved with a significant difference of mouse body weight in HFD groups by week 3 (p<0.01). The aggravated SLE pathogenesis in HFD mice was characterized by skin rash, proteinuria, IgG glomerular deposition with increased histopathology index in kidney, and splenomegaly (p<0.05). Interestingly, increased of Tfh cells were found in the spleen of HFD group. Conclusion Our results demonstrated that HFD-induced obesity with increase Tfh cells contributes to the acceleration of SLE progression and metabolic abnormalities. Changing eating habit or interventions reducing obesity could improve both SLE symptoms and metabolic inflammation, especially in genetically predisposed individuals.