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

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Borges, MC 
Oliveira, IO 
Freitas, DF 
Gigante, DP 


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 = 810−13; women: β = -0.31; 95% CI = -0.36, -0.25; P = 710−27), whereas gluteofemoral fat was positively associated with adiponectin concentration (men: β = 0.13 standard unit of log adiponectin per standard unit increase in gluteofemoral fat; 95% CI = 0.03, 0.22; P = 0.008; women: β = 0.24; 95% CI = 0.17, 0.31; P = 710−11). In the Mendelian randomization analysis, genetically-predicted 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 = 210−11), whereas genetically-predicted hip circumference was positively associated with blood adiponectin concentration (β = 0.17 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.



adiponectin, abdominal fat, subcutaneous fat, Mendelian randomization, body fat distribution, adiposity, adipokines

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International Journal of Epidemiology

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Oxford University Press
Medical Research Council (MC_UU_12015/2)
Medical Research Council (MC_UU_12015/1)
The study ‘Pelotas Birth Cohort, 1982’ is conducted by Postgraduate Program in Epidemiology at Universidade Federal de Pelotas with the collaboration of the Brazilian Public Health Association (ABRASCO). From 2004 to 2013, the Wellcome Trust supported the 1982 birth cohort study. The International Development Research Center, World Health Organization, Overseas Development Administration, European Union, National Support Program for Centers of Excellence (PRONEX), the Brazilian National Research Council (CNPq) and the Brazilian Ministry of Health supported previous phases of the study. M.C.B. receives financial support from the Brazilian National Research Council (CNPq) [144749/2014-9, 201498/2014-6 (Science Without Borders Program), and 163291/2015-2] and Coordenac¸~ao de Aperfeic¸oamento de Pessoal de Nıvel Superior (CAPES). K.K.O. is supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2].