Obesity-associated miR-199a/214 cluster inhibits adipose browning via PRDM16-PGC-1α transcriptional network

Linyun He, Mowei Tang, Ting Xiao, Hailan Liu, Wei Liu, Guangdi Li, Feng Zhang, Yalun Xiao, Zhiguang Zhou, Feng Liu, Fang Hu

Research output: Contribution to journalArticle

4 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2585-2600
Number of pages16
JournalDiabetes
Volume67
Issue number12
DOIs
StatePublished - Dec 1 2018

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Brown Adipocytes
Gene Regulatory Networks
Obesity
Thermogenesis
Gene Expression
Obese Mice
Peroxisomes
Brown Adipose Tissue
MicroRNAs
Adrenergic Receptors
Adipose Tissue
Respiration
Beige Adipocytes

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Obesity-associated miR-199a/214 cluster inhibits adipose browning via PRDM16-PGC-1α transcriptional network. / He, Linyun; Tang, Mowei; Xiao, Ting; Liu, Hailan; Liu, Wei; Li, Guangdi; Zhang, Feng; Xiao, Yalun; Zhou, Zhiguang; Liu, Feng; Hu, Fang.

In: Diabetes, Vol. 67, No. 12, 01.12.2018, p. 2585-2600.

Research output: Contribution to journalArticle

He, L, Tang, M, Xiao, T, Liu, H, Liu, W, Li, G, Zhang, F, Xiao, Y, Zhou, Z, Liu, F & Hu, F 2018, 'Obesity-associated miR-199a/214 cluster inhibits adipose browning via PRDM16-PGC-1α transcriptional network', Diabetes, vol. 67, no. 12, pp. 2585-2600. https://doi.org/10.2337/db18-0626
He, Linyun ; Tang, Mowei ; Xiao, Ting ; Liu, Hailan ; Liu, Wei ; Li, Guangdi ; Zhang, Feng ; Xiao, Yalun ; Zhou, Zhiguang ; Liu, Feng ; Hu, Fang. / Obesity-associated miR-199a/214 cluster inhibits adipose browning via PRDM16-PGC-1α transcriptional network. In: Diabetes. 2018 ; Vol. 67, No. 12. pp. 2585-2600.
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