Obesity-induced hypoadiponectinaemia: The opposite influences of central and peripheral fat compartments

Abstract

Background and Aims: The substantial reduction in adiponectin concentration among obese individuals seems to depend on fat distribution and is a marker of metabolic and adipose tissue dysfunction. We aimed to: (i) address whether abdominal fat from different compartments (visceral, deep subcutaneous abdominal and superficial subcutaneous abdominal) and gluteofemoral fat are independently associated with blood adiponectin concentration; and (ii) investigate whether abdominal (proxied by waist circumference) and gluteofemoral fat (proxied by hip circumference) accumulation causally determine blood adiponectin concentration. Methods: To investigate the independent association of abdominal and gluteofemoral fat with adiponectin concentration, we used multivariable regression and data from 30- year-old adults from the 1982 Pelotas Birth Cohort (n=2,743). To assess the causal role of abdominal and gluteofemoral fat accumulation on adiponectin concentration, we used Mendelian randomization and data from two consortia of genome-wide association studies-the GIANT (n > 210 000) and ADIPOGen consortia (n=29 347). Results: In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: β-0.24 standard unit of log adiponectin per standard unit increase in abdominal fat; 95% confidence interval (CI)=-0.31, -0.18; P=8*10-13; women: β-0.31; 95% CI=-0.36, -0.25; P=7*10-27), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: β0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI=0.03, 0.22; P=0.008; women: β0.24; 95% CI=0.17, 0.31; P=7*10-11). In the Mendelian randomization analysis, geneticallypredicted waist circumference was inversely related to blood adiponectin concentration (β-0.27 standard unit of log adiponectin per standard unit increase in waist circumference; 95% CI=-0.36, -0.19; P=2*10-11), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration (β0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI=0.11, 0.24; P=1*10-7). Conclusions: These results support the hypotheses that there is a complex interplay between body fat distribution and circulating adiponectin concentration, and that whereas obesity-induced hypoadiponectinaemia seems to be primarily attributed to abdominal fat accumulation, gluteofemoral fat accumulation is likely to exert a protective effect.