Serum GDF3 is Associated with Visceral Obesity, Insulin Resistance, and Inflammation in Non-Diabetic Adults: A Cross-Sectional Study with an Interventional Component.

PURPOSE: Growth differentiation factor 3 (GDF3), a TGFβ superfamily cytokine, has been linked to visceral adipose proliferation and adiposity in animal studies. However, the relationship between circulating GDF3 levels and visceral adiposity in humans remains unclear. This study aimed to assess the potential of serum GDF3 as a biomarker for visceral obesity.

PATIENTS AND

METHODS

This study comprised a cross-sectional component and an embedded self-controlled interventional component. A total of 282 adults aged 18-65 years were enrolled, including 162 individuals with visceral obesity and 120 without visceral obesity. Visceral obesity was defined as a visceral fat area (VFA) ≥ 100 cm2. In addition, 23 participants with visceral obesity completed a 12-week semaglutide weight-loss intervention with follow-up assessments. Serum levels of GDF3, IL-6, TNF-α and MCP-1 were measured by enzyme-linked immunosorbent assay. Correlation analyses, multivariable logistic regression, linear regression, and exploratory mediation analyses were performed to evaluate the associations of serum GDF3 with visceral obesity and related metabolic-inflammatory parameters.

RESULTS

Serum GDF3 levels were significantly higher in adults with visceral obesity than in those without visceral obesity (P < 0.001). Multivariable logistic regression showed that serum GDF3 was independently associated with visceral obesity. Moreover, after 12 weeks of semaglutide intervention, reductions in visceral fat were positively correlated with reduction in serum GDF3 levels (r = 0.437). Linear regression analyses indicated that, in addition to VFA, HOMA-IR, TNF-α, and MCP-1 were independently associated with serum GDF3 levels. Mediation analyses suggested that serum GDF3 may partially mediate the associations of VFA with MCP-1 and HOMA-IR.

CONCLUSION

GDF3 may be a circulating biomarker of visceral obesity and a potential mediator linking visceral fat accumulation to related insulin resistance and inflammatory disturbances.