MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network

Hongbin Zhang; Meiping Guan; Kristy L Townsend; Tian Lian Huang; Ding An; Xu Yan; Ruidan Xue; Tim J Schulz; Jonathon Winnay; Marcelo Mori; Michael F Hirshman; Karsten Kristiansen; John S Tsang; Andrew P White; Aaron M Cypess; Laurie J Goodyear; Yu-Hua Tseng

doi:10.15252/embr.201540837

MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network

Hongbin Zhang, Meiping Guan, Kristy L Townsend, Tian Lian Huang, Ding An, Xu Yan, Ruidan Xue, Tim J Schulz, Jonathon Winnay, Marcelo Mori, Michael F Hirshman, Karsten Kristiansen, John S Tsang, Andrew P White, Aaron M Cypess, Laurie J Goodyear, Yu-Hua Tseng

79 Citations (Scopus)

Abstract

Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of subcutaneous white fat upon cold exposure. miR-455 activates AMPKα1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together, the data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders.

Original language	English
Journal	E M B O Reports
Volume	16
Issue number	10
Pages (from-to)	1378-1393
Number of pages	16
ISSN	1469-221X
DOIs	https://doi.org/10.15252/embr.201540837
Publication status	Published - 1 Oct 2015

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Zhang, H., Guan, M., Townsend, K. L., Huang, T. L., An, D., Yan, X., Xue, R., Schulz, T. J., Winnay, J., Mori, M., Hirshman, M. F., Kristiansen, K., Tsang, J. S., White, A. P., Cypess, A. M., Goodyear, L. J., & Tseng, Y-H. (2015). MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network. E M B O Reports, 16(10), 1378-1393. https://doi.org/10.15252/embr.201540837

Zhang, H, Guan, M, Townsend, KL, Huang, TL, An, D, Yan, X, Xue, R, Schulz, TJ, Winnay, J, Mori, M, Hirshman, MF, Kristiansen, K, Tsang, JS, White, AP, Cypess, AM, Goodyear, LJ & Tseng, Y-H 2015, 'MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network', E M B O Reports, vol. 16, no. 10, pp. 1378-1393. https://doi.org/10.15252/embr.201540837

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title = "MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network",

abstract = "Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of subcutaneous white fat upon cold exposure. miR-455 activates AMPKα1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together, the data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders.",

author = "Hongbin Zhang and Meiping Guan and Townsend, {Kristy L} and Huang, {Tian Lian} and Ding An and Xu Yan and Ruidan Xue and Schulz, {Tim J} and Jonathon Winnay and Marcelo Mori and Hirshman, {Michael F} and Karsten Kristiansen and Tsang, {John S} and White, {Andrew P} and Cypess, {Aaron M} and Goodyear, {Laurie J} and Yu-Hua Tseng",

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T1 - MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network

AU - Zhang, Hongbin

AU - Guan, Meiping

AU - Townsend, Kristy L

AU - Huang, Tian Lian

AU - An, Ding

AU - Yan, Xu

AU - Xue, Ruidan

AU - Schulz, Tim J

AU - Winnay, Jonathon

AU - Mori, Marcelo

AU - Hirshman, Michael F

AU - Kristiansen, Karsten

AU - Tsang, John S

AU - White, Andrew P

AU - Cypess, Aaron M

AU - Goodyear, Laurie J

AU - Tseng, Yu-Hua

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N2 - Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of subcutaneous white fat upon cold exposure. miR-455 activates AMPKα1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together, the data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders.

AB - Brown adipose tissue (BAT) dissipates chemical energy as heat and can counteract obesity. MicroRNAs are emerging as key regulators in development and disease. Combining microRNA and mRNA microarray profiling followed by bioinformatic analyses, we identified miR-455 as a new regulator of brown adipogenesis. miR-455 exhibits a BAT-specific expression pattern and is induced by cold and the browning inducer BMP7. In vitro gain- and loss-of-function studies show that miR-455 regulates brown adipocyte differentiation and thermogenesis. Adipose-specific miR-455 transgenic mice display marked browning of subcutaneous white fat upon cold exposure. miR-455 activates AMPKα1 by targeting HIF1an, and AMPK promotes the brown adipogenic program and mitochondrial biogenesis. Concomitantly, miR-455 also targets the adipogenic suppressors Runx1t1 and Necdin, initiating adipogenic differentiation. Taken together, the data reveal a novel microRNA-regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders.

U2 - 10.15252/embr.201540837

DO - 10.15252/embr.201540837

M3 - Journal article

C2 - 26303948

SN - 1469-221X

VL - 16

SP - 1378

EP - 1393

JO - E M B O Reports

JF - E M B O Reports

IS - 10

ER -

MicroRNA-455 regulates brown adipogenesis via a novel HIF1an-AMPK-PGC1α signaling network

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