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.
Highlights
MicroRNAs target up to 60% of mammalian mRNAs [1,2] and have been demonstrated to play a key role in adipocyte differentiation, obesity, insulin sensitivity and risk of developing type 2 diabetes (T2D) in murine models [3,4,5,6]
We evaluated the associations between age, sex, birth weight and Body mass index (BMI); and the expression levels of miR-483-3p, miR-103 and miR-143 (Figure 1A)
Birth weight: We found a trend towards an association between miR-483-3p levels; a ~450 g increase in birth weight was associated with a 24% decrease in miR-483-3p levels
Summary
MicroRNAs (miRNAs) target up to 60% of mammalian mRNAs [1,2] and have been demonstrated to play a key role in adipocyte differentiation, obesity, insulin sensitivity and risk of developing type 2 diabetes (T2D) in murine models [3,4,5,6]. Duan et al have found single nucleotide polymorphisms (SNPs) in ~20% of human genomic pre-miRNA sequences [7]. It remains to be determined whether these SNPs have a functional role, some SNPs have been found to have an effect on the expression of the mature miRNA [8]. The importance of miR-103, miR-143 and miR-483-3p in human glucose and lipid metabolism, and the relative impact of genetic and environmental factors in the regulation of their expression, are undisclosed
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