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

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

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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. Access


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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).


AUTHOR INFORMATION AUTHORS AND AFFILIATIONS * 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 * University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France Emilie Montastier, Diane Beuzelin, Dominique Langin & Nathalie Viguerie * Departments of


Endocrinology, Toulouse University Hospitals, Metabolism and Nutrition, and Clinical Biochemistry, Toulouse, France Emilie Montastier & Dominique Langin * Institut National de la Santé


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


Médicale (Inserm), Clinical Investigation Center 1436, Toulouse, France Claire Thalamas * Toulouse University Hospitals, Clinical Investigation Center 1436, Toulouse, France Claire Thalamas


Authors * Emilie Montastier View author publications You can also search for this author inPubMed Google Scholar * Diane Beuzelin View author publications You can also search for this author


inPubMed Google Scholar * Frédéric Martins View author publications You can also search for this author inPubMed Google Scholar * Lucile Mir View author publications You can also search for


this author inPubMed Google Scholar * Marie-Adeline Marqués View author publications You can also search for this author inPubMed Google Scholar * Claire Thalamas View author publications


You can also search for this author inPubMed Google Scholar * Jason Iacovoni View author publications You can also search for this author inPubMed Google Scholar * Dominique Langin View


author publications You can also search for this author inPubMed Google Scholar * Nathalie Viguerie View author publications You can also search for this author inPubMed Google Scholar


CORRESPONDING AUTHOR Correspondence to Nathalie Viguerie. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they have no conflict of interest. ELECTRONIC SUPPLEMENTARY


MATERIAL SUPPLEMENTARY METHODS SUPPLEMENTARY FIGURE 1 SUPPLEMENTARY TABLE 1 SUPPLEMENTARY TABLE 2 SUPPLEMENTARY TABLE 3 SUPPLEMENTARY TABLE 4 RIGHTS AND PERMISSIONS Reprints and permissions


ABOUT THIS ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 09 April 2018 * Revised: 14 September 2018 * Accepted: 27 September 2018 * Published: 27


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