Effects of high fat diet-induced obesity on pathophysiology, immune cells, and therapeutic efficacy in systemic lupus erythematosus.

ABSTRACT

Prior studies have suggested a strong link between obesity and autoimmune diseases. This study aimed to evaluate the effects of high fat diet (HFD)-induced obesity on the disease pathogenesis, immune cell infiltration, and therapeutic efficacy in systemic lupus erythematosus (SLE). Treatment with methylprednisolone significantly increased the survival in the control diet group, but not in the HFD group. An HFD significantly increased the incidence of severe proteinuria and glucose intolerance. Regardless of the diet, treatment with methylprednisolone significantly decreased the serum levels of anti-dsDNA antibodies, IL-2, IL-10, and interferon γ-induced protein 10 (IP-10), and improved the renal pathology scores. Treatment with methylprednisolone significantly lowered the serum levels of IL-6, MCP-1, and TNF-α in the control diet group, but not in the HFD group. HFD significantly increased the proportions of CD45+ and M1 cells and significantly decreased the proportion of M2 cells in white adipose tissue; methylprednisolone treatment significantly rescued this effect. In the HFD group, methylprednisolone treatment significantly decreased the M1M2 and increased the Foxp3+RORγt+ cell in the spleen compared with the untreated group. These data improve our understanding of the effect of HFD on the therapeutic efficacy of corticosteroids in SLE treatment, which could have clinical implications.