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

Jette Bork-Jensen, Anne Cathrine Baun Thuesen, Claus Heiner Bang-Berthelsen, Louise Groth Grunnet, Flemming Pociot, Henning Beck-Nielsen, Susan E. Ozanne, Pernille Poulsen, Allan Vaag

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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.
Original languageEnglish
JournalGenes
Volume5
Issue number3
Pages (from-to)508-517
Number of pages10
ISSN2073-4425
DOIs
Publication statusPublished - 2014
Externally publishedYes

Keywords

  • Genetics
  • Genetics (clinical)
  • Human metabolism
  • Micrornas
  • Subcutaneous adipose tissue
  • Twins
  • glucose
  • hemoglobin A1c
  • microRNA
  • microRNA 103
  • microRNA 143
  • microrna 483 3p
  • triacylglycerol
  • unclassified drug
  • adult
  • age
  • aged
  • article
  • birth weight
  • body mass
  • cohort analysis
  • comparative study
  • controlled study
  • cross-sectional study
  • disease association
  • dizygotic twins
  • environmental factor
  • female
  • gene expression regulation
  • genetic association
  • glucose blood level
  • glucose metabolism
  • heredity
  • human
  • human tissue
  • insulin resistance
  • insulin sensitivity
  • lipid metabolism
  • major clinical study
  • male
  • monozygotic twins
  • obesity
  • phenotype
  • real time polymerase chain reaction
  • subcutaneous fat
  • trend study
  • micrornas
  • subcutaneous adipose tissue
  • human metabolism
  • twins
  • QH426-470
  • Biology (General)
  • QH301-705.5
  • Science
  • Q
  • GENETICS
  • SUBCUTANEOUS ADIPOSE
  • INSULIN-RESISTANCE
  • BIRTH-WEIGHT
  • MICRORNAS
  • GLUCOSE
  • OBESITY
  • ADIPOGENESIS
  • ASSOCIATION
  • MIRNA
  • DIET
  • Genetics - General
  • Genetics - Human
  • Clinical biochemistry - General methods and applications
  • Biochemistry studies - Lipids
  • Biochemistry studies - Carbohydrates
  • Metabolism - General metabolism and metabolic pathways
  • Blood - Blood and lymph studies
  • Blood - Blood cell studies
  • Gerontology
  • Animals, Chordates, Humans, Mammals, Primates, Vertebrates
  • adiposity
  • BMI
  • monozygotic twin
  • dizygotic twin
  • heritability estimate

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