Circulating Thrombospondin-1 and Endothelin-1 Levels Tend to Decline with Increasing Obesity Severity in Women: Evidence from a Pilot, Cross-Sectional Study.

Thrombospondin-1 (TSP1) is a multimeric glycoprotein that is increasingly recognized as a mediator of metabolic, thrombotic, and inflammatory processes. Although TSP1 expression has been associated with adipose tissue dysfunction and insulin resistance, the precise relationship with obesity severity remains unclear. Endothelin-1 (ET1), another important regulator of vascular homeostasis, may also contribute to obesity-related cardiometabolic risk, with evidence suggesting sex-specific differences, including delayed onset in women. The study aimed to investigate circulating TSP1 and ET1 levels in a cohort of nondiabetic obese female adults, evaluate their associations with metabolic and inflammatory parameters, and determine whether these markers differ according to obesity severity and related disease risk. Fifty-five nondiabetic women with obesity and no history of cardiovascular events were enrolled at the Endocrinology Unit ("R. Dulbecco" Univ. Hospital, Catanzaro, Italy). Anthropometric and clinical data, together with hematological and coagulation parameters and metabolic indices (HOMA-IR, HbA1c, and lipid profile), were evaluated. TSP1 and ET1 concentrations were measured using automated enzyme immunoassays (ELISAs). The participants were stratified by BMI (30-34.9 vs. ≥35 kg/m) into low-risk and moderate/high-risk obesity based on the WHO classification, and correlations between biomarkers and metabolic/inflammatory parameters were evaluated. The median BMI was 33.7 kg/m, with 52% of participants having moderate/high-risk obesity (WHO Class II/III). A significant proportion (69.8%) showed insulin resistance (HOMA-IR > 2.5). TSP1 was positively correlated with white blood cell count (WBC, r = 0.354, < 0.01), platelet count (PLT, r = 0.411, < 0.01), and glycated hemoglobin (r = 0.391, < 0.01), suggesting an association with both inflammation and glycemic control. ET1 was positively correlated with liver enzymes and triglycerides but negatively correlated with PLT and D-dimer. Women with moderate/high-risk obesity had significantly higher HOMA-IR, D-dimer, and inflammatory markers, in addition to a lower TSP1-to-PLT ratio. In this pilot study, TSP1 and ET1 levels tended to decrease with increasing obesity severity in women but were associated with distinct metabolic and inflammatory profiles. The results support the potential role of TSP1 as a biomarker for obesity-related cardiometabolic risk and highlight the complex interplay between TSP1, ET1, and obesity progression. Further studies may clarify whether targeting TSP1 can ameliorate chronic inflammation and insulin resistance in obesity and the potential sex-specific influences on these mechanisms.