Caloric Restriction Ameliorates Hypertension and Renal Injury in an Experimental Model of Systemic Lupus Erythematosus

Systemic Lupus Erythematosus (SLE) is a chronic multisystem autoimmune disorder characterized by a high risk for hypertension, renal injury, and cardiovascular disease. Evidence suggests that dietary interventions may have profound effects on autoimmune disease activity, including decreasing autoantibodies, improving renal injury, and increasing lifespan in murine SLE models. However, the impact of caloric restriction (CR) on hypertension is unknown. Thus, the present study tested the hypothesis that CR lowers blood pressure via an improvement in disease activity in a hypertensive mouse model of SLE, the NZBWF1 mouse. Beginning at 23 weeks of age, control (NZW, n=20) and SLE (NZBWF1, n=20) mice were individually housed to determine daily food intake for two weeks in order to determine caloric restriction during the experimental phase. In addition, baseline fecal pellets for metagenomic sequencing, blood for plasma and leukocyte analysis, and overnight urine for albuminuria determination were collected. Mice were then randomly assigned to the following groups (n=8-12 mice/group): Control-ad libitum, Control-30% caloric restriction, SLE-ad libitum, SLE-30% CR for eight weeks. EchoMRI body composition analyses revealed a significant reduction in fat mass in the SLE-CR group compared to the SLE-ad lib group (SLE-ad lib: 11.37±2.3 g vs. SLE-CR: 0.79±0.3 g, p<.0001). Albuminuria incidence, as assessed by urine dipstick analysis, was significantly lower (p < 0.05; Mantel-Cox test) in the SLE-CR group compared to the SLE-ad lib group over the experimental period. Furthermore, the urinary albumin excretion rate, as determined via an enzyme-linked immunosorbent assay (ELISA), was significantly lower in the SLE-CR group compared to SLE-ad lib at the end of the study (SLE-ad lib: 218±70 µg/day vs. SLE-CR 48±10 µg/day p = 0.0220). Vascular stiffness, measured using Doppler ultrasound of the aorta, was lower in SLE-CR mice after caloric restriction (SLE-ad lib: 3.7±0.3 vs. SLE-CR: 2.9±0.3 m/s, p=0.12). At the conclusion of the study, blood pressure was measured chronically using carotid artery catheter and showed that SLE mice who underwent CR had lower blood pressure (SLE-ad lib: 148.2±9.0 vs. SLE-CR: 132.4±3.5 mmHg, p=0.1347). The combination of reduced albuminuria, lower blood pressure, and decreased vascular stiffness suggests that CR may improve cardiovascular and renal health in the context of autoimmune disease. In future analyses, we will analyze circulating, renal, and adipose immune cell populations by flow cytometry and assess the impact of caloric restriction on gut microbial communities. NHLBI 5T32HL105324; NHLBI R00 HL146888; NHLBI U54HL169191; NIGMS P20GM104357; P30GM149404 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.