Visceral adipose tissue as a critical risk factor for patients with systemic lupus erythematous

Systemic lupus erythematosus (SLE) is associated with a markedly increased burden of cardiometabolic comorbidities, in particular premature cardiovascular disease driven by chronic inflammation, immune dysregulation, and excess visceral adiposity. Cross-sectional studies show that women with SLE have disproportionately elevated volumes of visceral and epicardial adipose tissue compared with matched controls, and that this dysfunctional fat depot correlates with adverse metabolic profiles, endothelial dysfunction, and markers of systemic inflammation. Despite this, visceral adiposity is rarely assessed systematically in lupus care, and targeted, non-pharmacologic interventions to reduce this modifiable risk factor remain largely unexplored. We hypothesize that a comprehensive lifestyle modification program targeting excess visceral adipose tissue and ectopic fat will improve the cardiometabolic profile, inflammatory status, physical fitness, and health-related quality of life of women living with SLE who are at high cardiometabolic risk. The long-term objective of this research is to establish visceral adiposity as a clinically actionable, reversible determinant of cardiovascular and global health outcomes in lupus, and to develop a scalable, precision lifestyle intervention that can be integrated into routine rheumatology practice. To test this hypothesis, we will conduct a 12‑month, single-arm pilot intervention in 20 middle-aged women with SLE characterized by abdominal obesity and the “hypertriglyceridemic waist” phenotype, recruited from an established, deeply phenotyped SARD biobank cohort. Specific Aim 1 is to determine whether a structured lifestyle program combining individualized nutritional counselling and supervised physical activity/exercise reduces visceral and ectopic adipose tissue, quantified by abdominal and cardiac MRI and hepatic proton magnetic resonance spectroscopy. Specific Aim 2 is to assess the impact of visceral fat reduction on cardiometabolic risk factors, including plasma lipids, apolipoprotein B, fasting glucose, insulin resistance (HOMA‑IR), blood pressure, and high-sensitivity C-reactive protein. Specific Aim 3 is to evaluate changes in cardiorespiratory fitness, objectively measured physical activity/sedentary behaviour, dietary quality, SLE-related symptoms, and patient-reported quality of life. Participants will undergo standardized assessments at baseline, 6 months, and 12 months, including anthropometry, dual-energy X‑ray absorptiometry, MRI/MRS-based quantification of abdominal, epicardial, pericardial, and liver fat, cardiopulmonary exercise testing, accelerometry, web-based dietary assessment, and lupus-specific clinical and questionnaire-based evaluations. The lifestyle intervention, delivered by an experienced multidisciplinary team in cardiometabolic risk management and lupus, emphasizes sustainable improvements in diet quality and progressive endurance exercise (approximately 150 minutes/week), tailored to individual capabilities and disease-related limitations. This project is highly relevant to lupus because it targets a central, modifiable driver of cardiovascular morbidity that is amplified in SLE by disease activity, treatment exposures (notably glucocorticoids), fatigue, and physical inactivity. By linking detailed imaging and inflammatory profiles to clinical and patient-reported outcomes, this pilot will generate mechanistic and feasibility data needed to design larger, controlled trials and to position waist circumference and visceral adiposity reduction as key elements of comprehensive SLE management.