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

Emilie Montastier, Diane Beuzelin, Frédéric Martins, Lucile Mir, Marie-Adeline Marqués, Claire Thalamas, Jason Iacovoni, Dominique Langin, Nathalie Viguerie
International Journal of Obesity. 2018-11-27; 43(7): 1485-1490
DOI: 10.1038/s41366-018-0260-5

1. Int J Obes (Lond). 2019 Jul;43(7):1485-1490. doi: 10.1038/s41366-018-0260-5.
Epub 2018 Nov 27.

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

Montastier E(1)(2)(3), Beuzelin D(1)(2), Martins F(1)(4), Mir L(1), Marqués
MA(1), Thalamas C(5)(6), Iacovoni J(1), Langin D(1)(2)(3), Viguerie N(7)(8).

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. .
(8)University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
.

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.