title: Vitamin D limits inflammation-linked microRNA expression in adipocytes in vitro and in vivo: A new mechanism for the regulation of inflammation by vitamin D.
abstract: Inflammation of adipose tissue is believed to be a contributing factor to many chronic diseases associated with obesity. Vitamin D (VD) is now known to limit this metabolic inflammation by decreasing inflammatory marker expression and leukocyte infiltration in adipose tissue. In this study, we investigated the impact of VD on microRNA (miR) expression in inflammatory conditions in human and mouse adipocytes, using high-throughput methodology (miRNA PCR arrays). Firstly, we identified three miRs (miR-146a, miR-150, and miR-155) positively regulated by TNFα in human adipocytes. Interestingly, the expression of these miRs was strongly prevented by 1,25(OH)2D preincubation. These results were partly confirmed in 3T3-L1 adipocytes (for miR-146a and miR-150). The ability of VD to control the expression of these miRs was confirmed in diet-induced obese mice: the levels of the three miRs were increased following high fat (HF) diet in epididymal white adipose tissue and reduced in HF diet fed mice supplemented with VD. The involvement of NF-κB signaling in the induction of these miRs was confirmed in vitro and in vivo using aP2-p65 transgenic mice. Finally, the ability of VD to deactivate NF-κB signaling, via p65 and IκB phosphorylation inhibition in murine adipocyte, was observed and could constitute a driving molecular mechanism. This study demonstrated for the first time that VD modulates the expression of miRs in adipocytes in vitro and in adipose tissue in vivo through its impact on NF-κB signaling pathway, which could represent a new mechanism of regulation of inflammation by VD.
authors.affiliation: a NORT , Aix-Marseille Université , INRA, INSERM, 13000 , Marseille , France.
authors.forename: Esma
authors.initials: E
authors.lastname: Karkeni
authors.affiliation: a NORT , Aix-Marseille Université , INRA, INSERM, 13000 , Marseille , France.
authors.forename: Lauriane
authors.initials: L
authors.lastname: Bonnet
authors.affiliation: a NORT , Aix-Marseille Université , INRA, INSERM, 13000 , Marseille , France.
authors.forename: Julie
authors.initials: J
authors.lastname: Marcotorchino
authors.affiliation: a NORT , Aix-Marseille Université , INRA, INSERM, 13000 , Marseille , France.
authors.forename: Franck
authors.initials: F
authors.lastname: Tourniaire
authors.affiliation: a NORT , Aix-Marseille Université , INRA, INSERM, 13000 , Marseille , France.
authors.forename: Julien
authors.initials: J
authors.lastname: Astier
authors.affiliation: b Pennington Biomedical Research Center , Louisiana State University System , Baton Rouge , Louisiana 70808 , USA.
authors.forename: Jianping
authors.initials: J
authors.lastname: Ye
authors.affiliation: a NORT , Aix-Marseille Université , INRA, INSERM, 13000 , Marseille , France.
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Landrier
mesh_terms: D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D002478:Cells, Cultured; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics*; D016328:NF-kappa B / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology*; D014815:Vitamins / Q000494:pharmacology*
chemical_list: D000893:Anti-Inflammatory Agents; D035683:MicroRNAs; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D014815:Vitamins; D014807:Vitamin D
keywords: Inflammation; NF-κB; aP2-p65 transgenic mice; adipocyte; miRs; vitamin D