@article{46b97635cd45489396f4a7e3fb0a047a,
title = "Obesity-associated miR-199a/214 cluster inhibits adipose browning via PRDM16-PGC-1α transcriptional network",
abstract = "miRNAs are important regulators of differentiation, development, and function of brown and beige fat cells. In this study, we identify the role of the miR-199a/214 cluster in the regulation of brown and beige adipocyte development and thermogenesis in vitro and in vivo. We show that expression of the miR-199a/214 cluster is dramatically decreased during brown and beige adipocyte differentiation and in response to cold exposure or β-adrenergic receptor activation. The cluster levels are significantly upregulated in the adipose tissues of obese mice and human subjects. Overexpression of the miR-199a/214 cluster suppresses brown adipocyte differentiation and inhibits thermogenic gene expression and mitochondrial respiration, whereas knockdown of the cluster increases thermogenic gene expression and mitochondrial function in beige adipocytes. In addition, inhibition of the miR-199a/214 cluster promotes beiging effects in vivo. We further show that miR-199a/214 suppresses brown adipocyte differentiation and beige fat development by directly targeting PRDM16 and peroxisome PGC-1α, two key transcriptional regulators of adipose browning. Together, these observations reveal that the miR-199a/214 cluster is a key negative regulator of brown and beige fat development and thermogenesis.",
author = "Linyun He and Mowei Tang and Ting Xiao and Hailan Liu and Wei Liu and Guangdi Li and Feng Zhang and Yalun Xiao and Zhiguang Zhou and Feng Liu and Fang Hu",
note = "Funding Information: Funding. This work was supported by grants from the National Natural Science Foundation of China (31471131 and 31871180) and the International Science and Technology Cooperation Program of China (2014DFG32490) to F.H., the National Basic Research Program of China (2014CB910501) to F.L., and the National Natural Science Foundation of China (31571368) and the Project of Innovation-Driven Plan of Central South University (2016CX031) to G.L. Duality of Interest. No potential conflicts of interest relevant to this article were reported. Author Contributions. L.H. and M.T. designed the study, carried out the research, and analyzed the results. T.X., H.L., F.Z., and Y.X. conducted the experiments. W.L. recruited and conducted the human studies. G.L. conducted bioinformatics analysis. Z.Z. and F.L. reviewed and edited the manuscript. F.H. supervised experiments, analyzed data, and wrote and revised the manuscript. F.H. is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2018 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license..",
year = "2018",
month = dec,
day = "1",
doi = "10.2337/db18-0626",
language = "English (US)",
volume = "67",
pages = "2585--2600",
journal = "Diabetes",
issn = "0012-1797",
publisher = "American Diabetes Association Inc.",
number = "12",
}