MicroRNA-193b Controls Adiponectin Production in Human White Adipose Tissue

MicroRNAs (miRNAs) are posttranscriptional regulators of gene expression. In white adipose tissue (WAT), recent studies suggest that miRNA levels are altered in various metabolic diseases, including obesity.

The objective of the study was to determine whether adipocyte-expressed miRNAs altered by obesity can regulate adiponectin expression/secretion in fat cells.

Eleven miRNAs previously shown to be altered in obese human WAT were overexpressed in human in vitro-differentiated adipocytes followed by assessments of adiponectin levels in conditioned media.

This was cohort study (n = 56) in an academic hospital.

Subcutaneous WAT was obtained from nonobese and obese individuals.

There were no interventions in this study.

Protein and mRNA levels of adiponectin were measured.

Of the 11 investigated miRNAs, three (miR-193b/-126/-26a) increased adiponectin secretion when overexpressed in human adipocytes. However, in human WAT only miR-193b expression correlated with adiponectin gene expression and homeostasis model assessment of insulin resistance. Moreover, quantitative PCR of miR-193b in both WAT and isolated adipocytes showed a significant association with serum adiponectin levels. Overexpression of miR-193b altered the gene expression of seven known adiponectin regulators. 3'-untranslated region reporter assays confirmed binding to cAMP-responsive element binding protein 5, nuclear receptor interacting protein 1, and nuclear transcription factor Yα. The effects of miR-193b on nuclear transcription factor Yα expression were confirmed at the protein level. Transfection with individual miRNA target protectors selective for nuclear transcription factor Yα and nuclear receptor interacting protein 1 abolished the stimulatory effect of miR-193b on adiponectin secretion.

In human adipocytes, miR-193b controls adiponectin production via pathways involving nuclear transcription factor Yα and possibly nuclear receptor interacting protein 1.