Literature DB >> 26020766

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

Yasmina Belarbi1, Niklas Mejhert1, Silvia Lorente-Cebrián1, Ingrid Dahlman1, Peter Arner1, Mikael Rydén1, Agné Kulyté1.   

Abstract

CONTEXT: 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.
OBJECTIVE: The objective of the study was to determine whether adipocyte-expressed miRNAs altered by obesity can regulate adiponectin expression/secretion in fat cells.
DESIGN: 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.
SETTING: This was cohort study (n = 56) in an academic hospital. PATIENTS: Subcutaneous WAT was obtained from nonobese and obese individuals.
INTERVENTIONS: There were no interventions in this study. MAIN OUTCOME MEASURE(S): Protein and mRNA levels of adiponectin were measured.
RESULTS: 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.
CONCLUSIONS: In human adipocytes, miR-193b controls adiponectin production via pathways involving nuclear transcription factor Yα and possibly nuclear receptor interacting protein 1.

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Year:  2015        PMID: 26020766     DOI: 10.1210/jc.2015-1530

Source DB:  PubMed          Journal:  J Clin Endocrinol Metab        ISSN: 0021-972X            Impact factor:   5.958


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