Numerous Genes in Loci Associated With Body Fat Distribution Are Linked to Adipose Function

Author:

Dahlman Ingrid1,Rydén Mikael1,Brodin David2,Grallert Harald345,Strawbridge Rona J.6,Arner Peter1

Affiliation:

1. Department of Medicine, Huddinge, Karolinska Institutet, Stockholm, Sweden

2. Department of Biosciences and Nutrition, Karolinska Institutet, Stockholm, Sweden

3. German Center for Diabetes Research (DZD), Neuherberg, Germany

4. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

5. Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany

6. Cardiovascular Genetics and Genomics Group, Atherosclerosis Research Unit, Department of Medicine, Solna, Karolinska Institutet, Stockholm, Sweden

Abstract

Central fat accumulation is a strong risk factor for type 2 diabetes. Genome-wide association studies have identified numerous loci associated with body fat distribution. The objectives of the current study are to examine whether genes in genetic loci linked to fat distribution can be linked to fat cell size and number (morphology) and/or adipose tissue function. We show, in a cohort of 114 women, that almost half of the 96 genes in these loci are indeed associated with abdominal subcutaneous adipose tissue parameters. Thus, adipose mRNA expression of the genes is strongly related to adipose morphology, catecholamine-induced lipid mobilization (lipolysis), or insulin-stimulated lipid synthesis in adipocytes (lipogenesis). In conclusion, the genetic influence on body fat distribution could be mediated via several specific alterations in adipose tissue morphology and function, which in turn may influence the development of type 2 diabetes.

Funder

Strategic Research Programme (SRP) in Diabetes at Karolinska Institutet

Center of Innovative Medicine

Swedish Research Council for Health, Working Life and Welfare

Stockholm Läns Landsting

Novo Nordisk Foundation

European Association for the Study of Diabetes/Eli Lilly Foundation

Swedish Diabetes Foundation

European Union/European Federation of Pharmaceutical Industries and Associations Innovative Medicines Initiative Joint Undertaking

Publisher

American Diabetes Association

Subject

Endocrinology, Diabetes and Metabolism,Internal Medicine

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