title: Genetic versus Non-Genetic Regulation of miR-103, miR-143 and miR-483-3p Expression in Adipose Tissue and Their Metabolic Implications-A Twin Study.
abstract: 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.
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. jbj@sund.ku.dk.
authors.forename: Jette
authors.initials: J
authors.lastname: Bork-Jensen
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. anne.cathrine.baun.thuesen@regionh.dk.
authors.forename: Anne Cathrine Baun
authors.initials: AC
authors.lastname: Thuesen
authors.affiliation: Department of Clinical and Experimental Research, Glostrup Research Institute, Glostrup University Hospital, DK-2600 Glostrup, Denmark. flemming.pociot.01@regionh.dk.
authors.forename: Claus Heiner
authors.initials: CH
authors.lastname: Bang-Bertelsen
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. louise.groth.grunnet@regionh.dk.
authors.forename: Louise Groth
authors.initials: LG
authors.lastname: Grunnet
authors.affiliation: Center for Non-Coding RNA in Technology and Health, Science, University of Copenhagen, DK-2000 Frederiksberg, Denmark. flemming.pociot.01@regionh.dk.
authors.forename: Flemming
authors.initials: F
authors.lastname: Pociot
authors.affiliation: Diabetes Research Center, Odense University Hospital, DK-5000 Odense C, Denmark. henning.beck-nielsen@ouh.regionsyddanmark.dk.
authors.forename: Henning
authors.initials: H
authors.lastname: Beck-Nielsen
authors.affiliation: 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. seo10@mole.bio.cam.ac.uk.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
authors.affiliation: Novo Nordisk, DK-2860 Bagsværd, Denmark. pepn@novonordisk.com.
authors.forename: Pernille
authors.initials: P
authors.lastname: Poulsen
authors.affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. allan.vaag@regionh.dk.
authors.forename: Allan
authors.initials: A
authors.lastname: Vaag