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Int J Obes (Lond). 2018 Nov 27. doi: 10.1038/s41366-018-0260-5. [Epub ahead of print]

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

Author information

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.
2
University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
3
Departments of Endocrinology, Toulouse University Hospitals, Metabolism and Nutrition, and Clinical Biochemistry, Toulouse, France.
4
Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Plateforme GeT (Génome et Transcriptome) du Génopole, Toulouse, France.
5
Institut National de la Santé et de la Recherche Médicale (Inserm), Clinical Investigation Center 1436, Toulouse, France.
6
Toulouse University Hospitals, Clinical Investigation Center 1436, Toulouse, France.
7
Institut National de la Santé et de la Recherche Médicale (Inserm), UMR1048, Obesity Research Laboratory, Institute of Metabolic and Cardiovascular Diseases (I2MC), Toulouse, France. nathalie.viguerie@inserm.fr.
8
University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France. nathalie.viguerie@inserm.fr.

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.

PMID:
30482933
DOI:
10.1038/s41366-018-0260-5

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