Specific Metabolic Markers Are Associated with Future Waist-Gaining Phenotype in Women

RESEARCH ARTICLE Specific Metabolic Markers Are Associated with Future Waist-Gaining Phenotype in Women Benedikt Merz1,10*, Ute Nöthlings1, Simone Wahl2,3,4, Marjolein Haftenberger5, Anja Schienkiewitz5, Jerzy Adamski6, Karsten Suhre7,8, Rui Wang-Sattler2, Harald Grallert2,3,4, Barbara Thorand3,4, Tobias Pischon9, Ursula Bachlechner10, Anna Floegel10, Annette Peters3,4, Heiner Boeing10 a11111 OPEN ACCESS Citation: Merz B, Nöthlings U, Wahl S, Haftenberger M, Schienkiewitz A, Adamski J, et al. (2016) Specific Metabolic Markers Are Associated with Future WaistGaining Phenotype in Women. PLoS ONE 11(6): e0157733. doi:10.1371/journal.pone.0157733 Editor: Guoying Wang, Johns Hopkins Bloomberg School of Public Health, UNITED STATES 1 Department of Nutrition and Food Sciences, University of Bonn, Bonn, Germany, 2 Research Unit of Molecular Epidemiology, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany, 3 Institute of Epidemiology II, Helmholtz Zentrum München – German Research Center for Environmental Health, Neuherberg, Germany, 4 German Center for Diabetes Research (DZD), Neuherberg, Germany, 5 Robert Koch-Institut, Department of Epidemiology and Health Monitoring, Berlin, Germany, 6 Institute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, 7 Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, 8 Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar, Doha, Qatar, 9 Molecular Epidemiology Research Group, Max Delbrück Center for Molecular Medicine (MDC), Berlin, Germany, 10 Department of Epidemiology, German Institute of Human Nutrition, PotsdamRehbruecke, Germany * Abstract Received: September 27, 2015 Accepted: June 4, 2016 Published: June 20, 2016 Copyright: © 2016 Merz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: For ethical considerations and legal restrictions the data of EPIC-Potsdam, DEGS and KORA cannot be made freely available in a public repository. Data from the EPIC-Potsdam study may be requested at the German Institute of Human Nutrition (contributing author Heiner Boeing). Data from the KORA study may be requested at the Helmholz Center Munich (corresponding author Simone Wahl). Data from the DEGS study may be requested at the Robert KochInstitut (contributing author Marjolein Haftenberger). Funding: BM, MH and UB were supported by the “Kompetenznetz Adipositas (Competence Network Objective Our study aims to identify metabolic markers associated with either a gain in abdominal (measured by waist circumference) or peripheral (measured by hip circumference) body fat mass. Methods Data of 4 126 weight-gaining adults (18–75 years) from three population-based, prospective German cohort studies (EPIC, KORA, DEGS) were analysed regarding a waist-gaining (WG) or hip-gaining phenotype (HG). The phenotypes were obtained by calculating the differences of annual changes in waist minus hip circumference. The difference was displayed for all cohorts. The highest 10% of this difference were defined as WG whereas the lowest 10% were defined as HG. A total of 121 concordant metabolite measurements were conducted using Biocrates AbsoluteIDQ1 kits in EPIC and KORA. Sex-specific associations with metabolite concentration as independent and phenotype as the dependent variable adjusted for confounders were calculated. The Benjamini-Hochberg method was used to correct for multiple testing. PLOS ONE | DOI:10.1371/journal.pone.0157733 June 20, 2016 1 / 18 Metabolic Determinants of Body Fat Distribution Obesity)” funded by the Federal Ministry of Education and Research (FKZ: 01GI1121B) (http://www. gesundheitsforschung-bmbf.de/de/2042.php). KS is supported by "Biomedical Research Program" funds at Weill Cornell Medical College in Qatar, a program funded by the Qatar Foundation. The KORA research platform (KORA, Cooperative Research in the Region of Augsburg) was initiated and financed by the Helmholtz Zentrum München - German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Research and by the State of Bavaria. Furthermore, KORA research was supported within the Munich Center of Health Sciences (MC Health), LudwigMaximilians-Universität, as part of LMUinnovativ. Competing Interests: The authors have declared that no competing interests exist. Results Across studies both sexes gained on average more waist than hip circumference. We could identify 12 metabolites as being associated with the WG (n = 8) or HG (n = 4) in men, but none were significant after correction for multiple testing; 45 metabolites were associated with the WG (n = 41) or HG (n = 4) in women. For WG, n = 21 metabolites remained significant after correction for multiple testing. Respective odds ratios (OR) ranged from 0.66 to 0.73 for tryptophan, the diacyl-phosphatidylcholines (PC) C32:3, C36:0, C38:0, C38:1, C42:2, C42:5, the acyl-alkyl-PCs C32:2, C34:0, C36:0, C36:1, C36:2, C38:0, C38:2, C40:1, C40:2, C40:5, C40:6, 42:2, C42:3 and lyso-PC C17:0. Conclusion Both weight-gaining men and women showed a clear tendency to gain more abdominal than peripheral fat. Gain of abdominal fat seems to be related to an initial metabolic state reflected by low concentrations of specific metabolites, at least in women. Thus, higher levels of specific PCs may play a protective role in gaining waist circumference. Introduction Overweight and obesity are major public health problems in Germany. More than two-thirds of the male and more than half of the female population were classified as overweight in a representative nationwide survey conducted between 2008 and 2011 [1]. Increased fat mass is associated with the risk of hypertension and an increased risk for type 2 diabetes, cardiovascular disease (CVD) and several types of cancer [2–4]. Body weight gain during adulthood independent of initial adult body mass index (BMI) was reported to be an independent risk factor for diabetes [5, 6] and is in general accompanied by an increase in total body fat. The distribution of body fat has been shown to be independently associated with chronic diseases [7–9] and a distinction should be made between abdominal and gluteofemoral phenotypes. Measurements of waist and hip circumference have been proven useful to assess body fat distribution [10, 11]. Waist circumference has been shown to be a good measure of visceral adipose tissue and abdominal obesity [12, 13]. Visceral fat, which surrounds the inner organs and increases with abdominal fat accumulation, is accompanied by unfavourable metabol (...truncated)