Caloric Restriction Decreases Autoimmune Disease Activity and Lowers Blood Pressure in an Experimental Model of Systemic Lupus Erythematosus

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that occurs more frequently and in women and is associated with an increased risk of renal injury and hypertension. Studies have shown that obesity is associated with greater SLE disease activity and is a significant modifiable risk factor for hypertension. Although dietary interventions such as vitamin D supplementation, omega-3 fatty acids, and macronutrient modification have been tested in autoimmune disease, little is known about how diet influences blood pressure in the setting of SLE. Caloric restriction (CR) has been shown to extend lifespan, delay nephritis, and reduce autoantibody production in murine models of SLE. However, its impact on hypertension and renal outcomes is poorly understood. In this study, we hypothesized that CR would ameliorate hypertension and renal injury in NZBWF1 mice, an established model of SLE. Female NZBWF1 and NZW control mice were subject to ad libitum (ADL) or 30% CR feeding for 8 weeks. CR mice had reduced body weight, plasma leptin levels, and autoantibody levels. CR mice also exhibited decreased albuminuria, urinary KIM-1, and renal B and T cell infiltration. CR mice had lower blood pressure, and the lower BP in SLE-CR mice neared significance in comparison to SLE-ADL. These findings demonstrate that CR tends to lower blood pressure and improves renal injury in NZBWF1 mice. Together, these results highlight the interplay between metabolic status, immune dysregulation, and renal complications in SLE, suggesting that CR may be a promising approach to mitigate end-organ damage in SLE-associated hypertension.