High Dietary Fat Promotes Visceral Obesity and Impaired Endothelial Function in Female Mice With Systemic Lupus Erythematosus

Abstract

Inflammation contributes to metabolic and cardiovascular disease. Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disorder that predominantly affects young women. Cardiovascular disease is a major cause of mortality in patients with SLE. We recently reported that a model of SLE (female New Zealand Black/White F1 [NZBWF1] mice) developed characteristics of the metabolic syndrome. In the present study, we tested the hypothesis that high dietary fat with SLE accelerated development of cardiovascular risk factors such as central obesity and vascular dysfunction. Twenty-four-week-old female SLE mice (NZBWF1) were fed either a control diet (SLE, 10% kcal) or a high-fat (HF) diet (SLE + HF, 45% kcal) for a total of 14 weeks. Body weight was similar between SLE (42 [1] g, n = 5) and SLE + HF (45 [2] g, n = 6) mice, and weight gain was not different in the SLE + HF mice (+18.0 [3.0]%) compared with controls (+15.8 [3.6]%); food intake was not different (SLE, 2.2 [0.3] vs SLE + HF, 2.1 [0.2] g/24 hours). At the end of the experiment, 57% of the SLE + HF mice exhibited signs of albuminuria (>100 mg/dL) compared with only 20% of the control SLE mice. Endothelial-dependent relaxation in isolated carotid arteries was impaired in the SLE + HF group compared with that in the SLE group. Ovarian fat increased in SLE + HF mice (6.6 [0.5] g) compared with that in the control SLE mice (5.4 [0.1] g, P < 0.05), and liver weight decreased in SLE + HF (1.6 [0.1] g) mice compared with that in control mice (1.9 [0.1] g, P < 0.03). These data suggest that dietary fat accelerates renal injury and peripheral vascular dysfunction and promotes visceral obesity in a disease model with chronic inflammation.