Plasma proteomes of obesity and allometric body shapes in the EPIC cohort

Abstract General obesity (high body mass index, BMI) affects circulating proteins. Obesity-related outcomes, however, differ by body shape but waist and hip circumferences cannot distinguish abdominal from general obesity. We therefore used the allometric body shape index (ABSI), waist-to-hip index (WHI) and hip index (HI), which factor out general obesity. We examined in linear regression models associations with 7289 protein markers (SomaScan) in 4037 EPIC cohort participants. One fifth of 2256 proteins associated with BMI were additionally independently associated with allometric abdominal obesity (418 with ABSI, 479 with WHI, same direction as BMI), and 38 proteins were associated with HI (predominantly opposite direction to BMI). Traditional body shape indices resembled BMI. Highest ranked proteins for ABSI and WHI were adiponectin (negative) and GHR (positive), for HI were TIMP4 and CD300LG (positive), whereas for BMI were leptin and FABP3 (positive). Only protein-coding genes for ABSI and WHI highlighted pathways of epithelial mesenchymal transition, xenobiotic metabolism and coagulation and genes upregulated in the liver, while protein-coding genes for BMI were upregulated in adipose tissue. Thus, allometric abdominal obesity and HI showed distinct proteomic profiles from general obesity, reflecting distinct pathophysiological mechanisms. Distinguishing abdominal from general obesity could help develop treatments targeting fat distribution.