Bork-Jensen, Jette9; Thuesen, Anne Cathrine Baun3; Bang-Bertelsen, Claus Heiner4; Grunnet, Louise Groth10; Pociot, Flemming11; Beck-Nielsen, Henning6; Ozanne, Susan E7; Poulsen, Pernille8; Vaag, Allan10
1 Section for Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet2 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet3 Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. email@example.com Department of Clinical and Experimental Research, Glostrup Research Institute, Glostrup University Hospital, DK-2600 Glostrup, Denmark. firstname.lastname@example.org Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet6 Diabetes Research Center, Odense University Hospital, DK-5000 Odense C, Denmark. email@example.com University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Level 4, Box 289, Addenbrookes Treatment Centre, Addenbrooke's Hospital, Cambridge CB2 0QQ, UK. firstname.lastname@example.org Novo Nordisk A/S9 Section for Metabolic Genetics, The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, Københavns Universitet10 Graduate School of Health and Medical Sciences, Faculty of Health and Medical Sciences, Københavns Universitet11 Department of Clinical Medicine, Department of Clinical Medicine, Faculty of Health and Medical Sciences, Københavns Universitet
Murine models suggest that the microRNAs miR-103 and miR-143 may play central roles in the regulation of subcutaneous adipose tissue (SAT) and development of type 2 diabetes (T2D). The microRNA miR-483-3p may reduce adipose tissue expandability and cause ectopic lipid accumulation, insulin resistance and T2D. We aimed to explore the genetic and non-genetic factors that regulate these microRNAs in human SAT, and to investigate their impact on metabolism in humans. Levels of miR-103, miR-143 and miR-483-3p were measured in SAT biopsies from 244 elderly monozygotic and dizygotic twins using real-time PCR. Heritability estimates were calculated and multiple regression analyses were performed to study associations between these microRNAs and measures of metabolism, as well as between these microRNAs and possible regulating factors. We found that increased BMI was associated with increased miR-103 expression levels. In addition, the miR-103 levels were positively associated with 2 h plasma glucose levels and hemoglobin A1c independently of BMI. Heritability estimates for all three microRNAs were low. In conclusion, the expression levels of miR-103, miR-143 and miR-483-3p in adipose tissue are primarily influenced by non-genetic factors, and miR-103 may be involved in the development of adiposity and control of glucose metabolism in humans.