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Adipocyte and Cell Biology

Niacin induces miR-502-3p expression which impairs insulin sensitivity in human adipocytes

International Journal of Obesity volume 43, pages 1485–1490 (2019)Cite this article

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Abstract

MicroRNAs have been involved in insulin resistance (IR). As the mechanism whereby niacin, an anti-dyslipidemic agent, leads to IR remains elusive, we sought to identify differentially expressed microRNAs in adipose tissue (AT) of individuals receiving niacin and to explore the link between microRNAs, niacin and IR in human adipocytes.

In a double-blind controlled study, 22 obese men received extended-release niacin or placebo over 8 weeks. Bioclinical data and subcutaneous AT biopsies were obtained before and after treatment. AT microRNA expression profiles were determined using RTqPCR for 758 human-specific microRNAs. hMADS adipocytes were treated with niacin, or acipimox (a niacin-like drug without effect on IR), or transfected with miR-502-3p. Glucose uptake and Western blotting were performed.

In obese men, insulin sensitivity decreased after niacin treatment. In AT, the expression of 6 microRNAs including miR-502-3p was up-regulated. Treatment of hMADS adipocytes with niacin specifically increased miR-502-3p expression. Acipimox had no effect. Overexpression of miR-502-3p in adipocytes led to reduced insulin-induced glucose uptake and lower insulin-stimulated AKT phosphorylation.

Long term niacin treatment altered microRNA expression levels in human AT. Increased miR-502-3p expression may play a role in the mediation of IR due to niacin in adipocytes.

The study is registered in Clinical Trials NCT01083329 and EudraCT 2009-012124-85.

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Acknowledgements

We thank GeT-TQ platform for technical support. DL is a member of Institut Universitaire de France.

Funding

The work was supported by grants from the National Research Agency ANR-09-GENO-0018-01 (to D. Langin), Inserm DHOS Recherche Translationnelle 2009 (to D. Langin), AOL-0816302 Hôpitaux de Toulouse (to D. Langin), Glaxo Smith Kline (to D. Langin), and JPI HDHL-miRDiet (to N.Viguerie and D. Langin).

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Authors and Affiliations

  1. Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France

    Emilie Montastier, Diane Beuzelin, Frédéric Martins, Lucile Mir, Marie-Adeline Marqués, Jason Iacovoni, Dominique Langin & Nathalie Viguerie

  2. University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France

    Emilie Montastier, Diane Beuzelin, Dominique Langin & Nathalie Viguerie

  3. Departments of Endocrinology, Toulouse University Hospitals, Metabolism and Nutrition, and Clinical Biochemistry, Toulouse, France

    Emilie Montastier & Dominique Langin

  4. Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Plateforme GeT (Génome et Transcriptome) du Génopole, Toulouse, France

    Frédéric Martins

  5. Institut National de la Santé et de la Recherche Médicale (Inserm), Clinical Investigation Center 1436, Toulouse, France

    Claire Thalamas

  6. Toulouse University Hospitals, Clinical Investigation Center 1436, Toulouse, France

    Claire Thalamas

Authors
  1. Emilie Montastier
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  2. Diane Beuzelin
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  4. Lucile Mir
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  7. Jason Iacovoni
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  9. Nathalie Viguerie
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Correspondence to Nathalie Viguerie.

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Montastier, E., Beuzelin, D., Martins, F. et al. Niacin induces miR-502-3p expression which impairs insulin sensitivity in human adipocytes. Int J Obes 43, 1485–1490 (2019). https://doi.org/10.1038/s41366-018-0260-5

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  • DOI: https://doi.org/10.1038/s41366-018-0260-5

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