WISP-1 in Obesity and Metabolic Dysfunction: The Modulatory Role of Exercise Training- A Narrative Review

Abstract

Obesity is a major global health concern strongly associated with metabolic disorders, chronic low-grade inflammation, insulin resistance, and an increased risk of cardiovascular disease. Among the emerging biomarkers implicated in obesity-related metabolic dysfunction, Wnt1-inducible signaling pathway protein-1 (WISP-1), a matricellular protein belonging to the CCN (Cyr61, C: Cyr61(Cysteine-rich angiogenic inducer 61/ C: CTGF (Connective Tissue Growth Factor), N: NOV (Nephroblastoma Overexpressed gene) family, has attracted increasing attention. WISP-1 is involved in tissue remodeling, extracellular matrix regulation, inflammatory signaling, and metabolic processes, and accumulating evidence suggests that elevated circulating levels are associated with visceral adiposity, insulin resistance, and systemic inflammation. Physical activity is widely recognized as a cornerstone intervention for improving metabolic health and reducing obesity-related complications. Exercise training modulates adipose tissue function, inflammatory pathways, insulin signaling, and extracellular matrix remodeling mechanisms that may be linked to alterations in WISP-1 expression. However, the extent to which exercise directly regulates WISP-1 remains incompletely understood, and existing findings are not entirely consistent across populations and intervention types. This narrative review synthesizes current evidence regarding the relationship between physical activity and WISP-1 levels in individuals with obesity. Available studies suggest that aerobic training, resistance exercise, and high-intensity interval training (HIIT) may reduce circulating WISP-1 concentrations, often in parallel with improvements in insulin sensitivity, body composition, and inflammatory markers. Nevertheless, the number of interventional studies remains limited, sample sizes are generally small, and methodological heterogeneity complicates definitive interpretation. Furthermore, much of the mechanistic understanding linking WISP-1 to insulin resistance derives from experimental or associative human data, highlighting the need for cautious interpretation of causality. Variations in exercise modality, intensity, duration, and participant characteristics may influence WISP-1 responses, underscoring the complexity of its regulation. Overall, while emerging evidence supports a potential link between exercise-induced metabolic improvements and modulation of WISP-1, well-designed longitudinal and mechanistic studies are required to clarify its physiological role and determine whether WISP-1 can serve as a reliable biomarker or therapeutic target in obesity related metabolic dysfunction.