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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.

Bork-Jensen J, Thuesen AC, Bang-Bertelsen CH, Grunnet LG, Pociot F, Beck-Nielsen H, Ozanne SE, Poulsen P, Vaag A - Genes (Basel) (2014)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. jbj@sund.ku.dk.

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.

No MeSH data available.


Related in: MedlinePlus

Multivariate analyses were performed to study the association between (A) age, birth weight, BMI and sex and miR-103, miR-143 and miR-483-3p expression in adipose tissue from elderly twins and the association between (B) miR-103, miR-143 and miR-483-3p and 2 h glucose values after an oral glucose tolerance test, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR) and triglycerides shown for all subjects (black), dizygotic (DZ) twins (blue) and monozygotic (MZ) twins (orange). Effect measures were transformed to percent wise changes per standard deviation (SD). Mean effects are shown by ●. Error bars represent the 95% confidence interval. All analyses were adjusted for age, sex and BMI. In addition the analyses of age, BMI and sex were adjusted for birth weight. Analyses involving all subjects (black) were additionally adjusted for twin and zygosity status. A p-value of ≤0.05 was considered significant, and is indicated by *. Body mass index (BMI), plasma glucose measured at 2 h in an oral glucose tolerance test (2 h glucose), homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c).
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genes-05-00508-f001: Multivariate analyses were performed to study the association between (A) age, birth weight, BMI and sex and miR-103, miR-143 and miR-483-3p expression in adipose tissue from elderly twins and the association between (B) miR-103, miR-143 and miR-483-3p and 2 h glucose values after an oral glucose tolerance test, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR) and triglycerides shown for all subjects (black), dizygotic (DZ) twins (blue) and monozygotic (MZ) twins (orange). Effect measures were transformed to percent wise changes per standard deviation (SD). Mean effects are shown by ●. Error bars represent the 95% confidence interval. All analyses were adjusted for age, sex and BMI. In addition the analyses of age, BMI and sex were adjusted for birth weight. Analyses involving all subjects (black) were additionally adjusted for twin and zygosity status. A p-value of ≤0.05 was considered significant, and is indicated by *. Body mass index (BMI), plasma glucose measured at 2 h in an oral glucose tolerance test (2 h glucose), homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c).

Mentions: We evaluated the associations between age, sex, birth weight and BMI; and the expression levels of miR-483-3p, miR-103 and miR-143 (Figure 1A). Age: We found that a ~5 year increase in age was associated with a ~33% decrease in miR-483-3p levels (p = 0.05) and with a 77% increase in miR-143 levels (p = 0.02). Sex: There were no statistically significant associations between sex and the expression levels of the miRNAs. 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. This effect was, however, not statistically significant (p = 0.09). BMI: We found that an increase of 3.7 kg/m2 in BMI was associated with a 34% increase in miR-103 expression (p = 0.05).


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.

Bork-Jensen J, Thuesen AC, Bang-Bertelsen CH, Grunnet LG, Pociot F, Beck-Nielsen H, Ozanne SE, Poulsen P, Vaag A - Genes (Basel) (2014)

Multivariate analyses were performed to study the association between (A) age, birth weight, BMI and sex and miR-103, miR-143 and miR-483-3p expression in adipose tissue from elderly twins and the association between (B) miR-103, miR-143 and miR-483-3p and 2 h glucose values after an oral glucose tolerance test, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR) and triglycerides shown for all subjects (black), dizygotic (DZ) twins (blue) and monozygotic (MZ) twins (orange). Effect measures were transformed to percent wise changes per standard deviation (SD). Mean effects are shown by ●. Error bars represent the 95% confidence interval. All analyses were adjusted for age, sex and BMI. In addition the analyses of age, BMI and sex were adjusted for birth weight. Analyses involving all subjects (black) were additionally adjusted for twin and zygosity status. A p-value of ≤0.05 was considered significant, and is indicated by *. Body mass index (BMI), plasma glucose measured at 2 h in an oral glucose tolerance test (2 h glucose), homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4198914&req=5

genes-05-00508-f001: Multivariate analyses were performed to study the association between (A) age, birth weight, BMI and sex and miR-103, miR-143 and miR-483-3p expression in adipose tissue from elderly twins and the association between (B) miR-103, miR-143 and miR-483-3p and 2 h glucose values after an oral glucose tolerance test, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR) and triglycerides shown for all subjects (black), dizygotic (DZ) twins (blue) and monozygotic (MZ) twins (orange). Effect measures were transformed to percent wise changes per standard deviation (SD). Mean effects are shown by ●. Error bars represent the 95% confidence interval. All analyses were adjusted for age, sex and BMI. In addition the analyses of age, BMI and sex were adjusted for birth weight. Analyses involving all subjects (black) were additionally adjusted for twin and zygosity status. A p-value of ≤0.05 was considered significant, and is indicated by *. Body mass index (BMI), plasma glucose measured at 2 h in an oral glucose tolerance test (2 h glucose), homeostatic model assessment of insulin resistance (HOMA-IR), hemoglobin A1c (HbA1c).
Mentions: We evaluated the associations between age, sex, birth weight and BMI; and the expression levels of miR-483-3p, miR-103 and miR-143 (Figure 1A). Age: We found that a ~5 year increase in age was associated with a ~33% decrease in miR-483-3p levels (p = 0.05) and with a 77% increase in miR-143 levels (p = 0.02). Sex: There were no statistically significant associations between sex and the expression levels of the miRNAs. 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. This effect was, however, not statistically significant (p = 0.09). BMI: We found that an increase of 3.7 kg/m2 in BMI was associated with a 34% increase in miR-103 expression (p = 0.05).

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Endocrinology, Diabetes and Metabolism, Rigshospitalet, DK-2200 Copenhagen N, Denmark. jbj@sund.ku.dk.

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.

No MeSH data available.


Related in: MedlinePlus