Obesity-induced Hypoadiponectinaemia: the Opposite Influences of Central and Peripheral Fat Compartments

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. 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). In the multivariable regression analysis, all abdominal fat depots were negatively associated with adiponectin concentration, specially visceral abdominal fat [men: beta = -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: beta = -0.31; 95% CI = -0.36, -0.25; P = 7*10(-27)), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: beta = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; P = 0.008; women: beta = 0.24; 95% CI = 0.17, 0.31; P = 7*10(-11)). In the Mendelian randomization analysis, genetically-predicted waist circumference was inversely related to blood adiponectin concentration (beta = -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 (beta = 0.17 standard unit of log adiponectin per standard unit increase in hip circumference; 95% CI = 0.11, 0.24; P = 1*10(-7)). 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.