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

$\textbf{Background and Aims:}$ 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. $\textbf{Methods:}$ 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). $\textbf{Results:}$ 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$^{-7}$). $\textbf{Conclusions:}$ 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.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]

Role of Adiponectin in Coronary Heart Disease Risk: A Mendelian Randomization Study

RATIONALE: Hypoadiponectinemia correlates with several coronary heart disease (CHD) risk factors. However, it is unknown whether adiponectin is causally implicated in CHD pathogenesis. OBJECTIVE: We aimed to investigate the causal effect of adiponectin on CHD risk. METHODS AND RESULTS: We undertook a Mendelian randomization study using data from genome-wide association studies consortia. We used the ADIPOGen consortium to identify genetic variants that could be used as instrumental variables for the effect of adiponectin. Data on the association of these genetic variants with CHD risk were obtained from CARDIoGRAM (22 233 CHD cases and 64 762 controls of European ancestry) and from CARDIoGRAMplusC4D Metabochip (63 746 cases and 130 681 controls; ≈ 91% of European ancestry) consortia. Data on the association of genetic variants with adiponectin levels and with CHD were combined to estimate the influence of blood adiponectin on CHD risk. In the conservative approach (restricted to using variants within the adiponectin gene as instrumental variables), each 1 U increase in log blood adiponectin concentration was associated with an odds ratio for CHD of 0.83 (95% confidence interval, 0.68–1.01) in CARDIoGRAM and 0.97 (95% confidence interval, 0.84–1.12) in CARDIoGRAMplusC4D Metabochip. Findings from the liberal approach (including variants in any locus across the genome) indicated a protective effect of adiponectin that was attenuated to the null after adjustment for known CHD predictors. CONCLUSIONS: Overall, our findings do not support a causal role of adiponectin levels in CHD pathogenesis

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

$\textbf{Background and Aims:}$ 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. $\textbf{Methods:}$ 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). $\textbf{Results:}$ 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$^{-7}$). $\textbf{Conclusions:}$ 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.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]

Numerical and experimental analysis of wrinkling during the cup drawing of an AA5042 aluminium alloy

The recent trend to reduce the thickness of metallic sheets used in forming processes strongly increases the likelihood of the occurrence of wrinkling. Thus, in order to obtain defect-free components, the prediction of this kind of defect becomes extremely important in the tool design and selection of process parameters. In this study, the sheet metal forming process proposed as a benchmark in the Numisheet 2014 conference is selected to analyse the influence of the tool geometry on wrinkling behaviour, as well as the reliability of the developed numerical model. The side-wall wrinkling during the deep drawing process of a cylindrical cup in AA5042 aluminium alloy is investigated through finite element simulation and experimental measurements. The material plastic anisotropy is modelled with an advanced yield criterion beyond the isotropic (von Mises) material behaviour. The results show that the shape of the wrinkles predicted by the numerical model is strongly affected by the finite element mesh used in the blank discretization. The accurate modelling of the plastic anisotropy of the aluminium alloy yields numerical results that are in good agreement with the experiments, particularly the shape and location of the wrinkles. The predicted punch force evolution is strongly influenced by the friction coefficient used in the model. Moreover, the two punch geometries provide drawn cups with different wrinkle waves, mainly differing in amplitude.The authors gratefully acknowledge the financial support of the Portuguese Foundation for Science and Technology (FCT) under project PTDC/EMS-TEC/1805/2012. The first author is also grateful to the FCT for the Postdoctoral grant SFRH/BPD/101334/2014 and P.D. Barros is grateful to the FCT for the PhD Grant SFRH/BD/98545/2013info:eu-repo/semantics/publishedVersio