@article{54361cbc3b804528b6df25c9d85bad4e,
title = "MiR-26 suppresses adipocyte progenitor differentiation and fat production by targeting Fbxl19",
abstract = "Fat storage in adult mammals is a highly regulated process that involves the mobilization of adipocyte progenitor cells (APCs) that differentiate to produce new adipocytes. Here we report a role for the broadly conserved miR-26 family of microRNAs (miR-26a-1, miR-26a-2, and miR-26b) as major regulators of APC differentiation and adipose tissue mass. Deletion of all miR-26-encoding loci in mice resulted in a dramatic expansion of adipose tissue in adult animals fed normal chow. Conversely, transgenic overexpression of miR-26a protected mice from high-fat diet-induced obesity. These effects were attributable to a cell-autonomous function of miR-26 as a potent inhibitor of APC differentiation. miR-26 blocks adipogenesis, at least in part, by repressing expression of Fbxl19, a conserved miR-26 target without a previously known role in adipocyte biology that encodes a component of SCF-type E3 ubiquitin ligase complexes. These findings have therefore revealed a novel pathway that plays a critical role in regulating adipose tissue formation in vivo and suggest new potential therapeutic targets for obesity and related disorders.",
keywords = "Adipocyte progenitor cell, Adipogenesis, Fbxl19, MiR-26, MicroRNA, Obesity, White adipose tissue",
author = "Asha Acharya and Berry, {Daniel C.} and He Zhang and Yuwei Jiang and Jones, {Benjamin T.} and Hammer, {Robert E.} and Graff, {Jonathan M.} and Mendell, {Joshua T.}",
note = "Funding Information: We thank Pierre Chambon for mouse strains, Feng Zhang for plasmids, Jeanetta Marshburn-Wynn and Frank Gillett for assistance with mouse husbandry, Mylinh Nguyen and the University of Texas Southwestern Transgenic Core for mouse generation, Vanessa Schmid and the McDermott Center Next-Generation Sequencing Core for high-throughput sequencing, Ruth Gordillo and Syann Lee at the University of Texas Southwestern Metabolic Phenotyping Core for phenotypic analyses, Angie Mobley and the University of Texas Southwestern Flow Cytometry Core for cell sorting, and Kathryn O{\textquoteright}Donnell and members of the Mendell laboratory for helpful comments on the manuscript. This work was supported by grants from Cancer Prevention and Research Institute of Texas (RP160249 to J.T.M.; RP150596 to the University of Texas Southwestern Bioinformatics Core Facility), National Institutes of Health (R35CA197311, P30CA142543, and P50CA196516 to J.T.M., and K01DK109027 to D.C.B.), and the Welch Foundation (I-1961-20180324 to J.T.M.). J.T.M. is an Investigator of the Howard Hughes Medical Institute. Publisher Copyright: {\textcopyright} 2019 Acharya et al. This article is distributed exclusively by Cold Spring Harbor Laboratory Press for the first six months after the full-issue publication date (see http://genesdev.cshlp.org/site/misc/terms.xhtml). After six months, it is available under a Creative Commons License (Attribution-NonCommercial 4.0 International), as described at http://creativecommons.org/licenses/by-nc/4.0/.",
year = "2019",
month = oct,
day = "1",
doi = "10.1101/gad.328955.119",
language = "English (US)",
volume = "33",
pages = "1367--1380",
journal = "Genes and Development",
issn = "0890-9369",
publisher = "Cold Spring Harbor Laboratory Press",
number = "19-20",
}