Session: SAT-LB-Late-Breaking Poster Session 1
Bench to Bedside
Poster Board SAT-LB-04
Methods: We performed a cross-sectional analysis of 2473 ambulatory, community-dwelling men ages ≥65 years enrolled in the Osteoporotic Fractures in Men Study from 6 sites in the U.S. The categorization of obese (BMI≥30), overweight (BMI 25.0-29.9) and normal weight (BMI 18.5-24.9) was based on WHO criteria. High-throughput quantitative proteomic analysis was performed on serum samples using a multi-dimensional approach coupling liquid chromatography, ion-mobility separation, and mass spectrometry (LC-IMS-MS). Peptides that were differentially abundant in obese versus normal weight men were identified using analysis of covariance adjusted for multiple comparisons using the Storey method with a false discovery rate (FDR) q-value < 0.05. Models also included adjustments for age, site, comorbidities, lifestyle factors, and medication use. Meta-analytic methods accounting for correlated metrics were used to generate protein-obesity association rankings from averaged differential abundance and combined p-values for peptides of each protein.
Results: Among the older men, 536 (21.7%) were obese and 650 (26.3%) were of normal weight. Of 18485 identified serum peptides, 1237 were associated with obesity in fully adjusted models with a q-value<0.05, and these peptides mapped to 169 proteins with a q-value < 0.05. Among these proteins were well-known markers of obesity: obese men had a higher abundance of C-reactive protein (q-value=0.003) and a lower abundance of adiponectin (q-value=0.005). The 5 top-ranking proteins associated with obesity were zinc-alpha-2 glycoprotein (ZAG2), glutathione peroxidase 3 (GPX3), vitamin D-binding protein (DBP), putative zinc-alpha-2-glycoprotein-like 1 (ZAGL1), and afamin. Obese men had 20-26% lower abundance of ZAG2, GPX3, DBP, and ZAGL1, and 34% higher abundance of afamin compared to normal weight men, q-values<10-10.
Conclusion: We have demonstrated a rapid and broad assessment of peptides and proteins associated with obesity using a novel, population-based proteomic approach. Traditional obesity markers like C-reactive protein were identified, and our findings support prior reports of decreased ZAG2 and GPX3 expression in adipose tissue of obese subjects and gene polymorphisms in DBP associated with high adiposity. Among the top ranking 5 proteins were 2 not previously reported with obesity, afamin and ZAGL1. Further research to understand the biologic roles of these proteins in obesity is needed.
Nothing to Disclose: CGL, AB, RS, EB, VP, PMC, DCB, DG, AB, SM, JL, ESO
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