Effects of Genetic Loci Associated with Central Obesity on Adipocyte Lipolysis.
Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis.



Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7-62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score.



The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis.



This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes.
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Rona J
RJ
Strawbridge
Chair of Nutritional Medicine, Else Kröner-Fresenius-Center for Nutritional Medicine and ZIEL-Research Center for Nutrition and Food Sciences, Technische Universität München, Munich, Germany.|Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Helmholtz Zentrum Muenchen and Technische Universität München, Munich, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.|Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
Helmut
H
Laumen
Atherosclerosis Research Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Anders
A
Hamsten
German Center for Diabetes Research (DZD), Neuherberg, Germany.|Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
Michaela
M
Breier
German Center for Diabetes Research (DZD), Neuherberg, Germany.|Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.|Institute of Epidemiology II, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, Neuherberg, Germany.
Harald
H
Grallert
Chair of Nutritional Medicine, Else Kröner-Fresenius-Center for Nutritional Medicine and ZIEL-Research Center for Nutrition and Food Sciences, Technische Universität München, Munich, Germany.|Clinical Cooperation Group Nutrigenomics and Type 2 Diabetes, Helmholtz Zentrum Muenchen and Technische Universität München, Munich, Germany.|German Center for Diabetes Research (DZD), Neuherberg, Germany.|Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universität Muenchen, Munich, Germany.
Hans
H
Hauner
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Peter
P
Arner
Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden.
Ingrid
I
Dahlman
D017667:Adipocytes / Q000378:metabolism*; D000293:Adolescent; D015992:Body Mass Index; D005260:Female; D006801:Humans; D008066:Lipolysis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D056128:Obesity, Abdominal / Q000235:genetics / Q000473:pathology*; D020641:Polymorphism, Single Nucleotide