Growth Differentiation Factor-15 Is Associated With Soluble Prorenin Receptor in Young Women With Increased Adiposity

Objective: Obesity in young adults is a global health concern, highlighting the urgent need to identify molecular biomarkers involved in its pathophysiology to inform therapeutic interventions. Growth differentiation factor-15 (GDF-15), a stress-responsive cytokine and the soluble prorenin receptor (s(P)RR), a component of the renin-angiotensin system (RAS), are independently associated with obesity, yet their interaction in young adults with varying adiposity status remains underexplored. We aimed to a) compare GDF-15 and s(P)RR levels between groups stratified by adiposity status and sex; and b) explore associations between GDF-15 and s(P)RR levels in groups stratified according to adiposity and sex. Design and method: This cross-sectional study included 1096 young adults aged 20-30 years, stratified by body mass index categories within each sex group, men (normal weight (n=292), overweight (n=161), and obese (n=71)) and women (normal weight (n=293), overweight (n=158), and obese (n=121)). All participants had no history or clinical evidence of cardiovascular disease at the screening phase. GDF-15 and s(P)RR levels were measured in serum. Results: Serum GDF-15 levels were comparable between the normal weight, overweight and obese groups in men (p=0.43) and women (p=0.07). However, s(P)RR levels were higher in both obese men (p<0.001) and women (p=0.001) compared to their normal weight and overweight counterparts. In a fully adjusted model, GDF-15 was positively associated with s(P)RR in both overweight (beta-coefficient=0.33, p=0.001) and obese women (beta-coefficient=0.21, p=0.027). When kidney function (estimated glomerular filtration rate (eGFR)) was adjusted for, the relationship remained significant in overweight women only (beta-coefficient=0.23, p=0.027). Conclusions: In young adults, s(P)RR levels were higher in obese men and women compared to their normal weight and overweight counterparts, while s(P)RR was positively associated with GDF-15 in overweight and obese women, but not in men. After adjusting for eGFR, this association was no longer evident in obese women, indicating that kidney function may contribute to this relationship in obese women. Our results may reflect early involvement of RAS in metabolic alterations among women with increased adiposity, highlighting sex-specific patterns which could improve targeted obesity prevention strategies.