Premium
Micro RNA ‐455 regulates brown adipogenesis via a novel HIF 1an‐ AMPK ‐ PGC 1α signaling network
Author(s) -
Zhang Hongbin,
Guan Meiping,
Townsend Kristy L,
Huang Tian Lian,
An Ding,
Yan Xu,
Xue Ruidan,
Schulz Tim J,
Winnay Jonathon,
Mori Marcelo,
Hirshman Michael F,
Kristiansen Karsten,
Tsang John S,
White Andrew P,
Cypess Aaron M,
Goodyear Laurie J,
Tseng YuHua
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201540837
Subject(s) - guan , medicine , gerontology , physiology , biology , genetics
Brown adipose tissue ( BAT ) dissipates chemical energy as heat and can counteract obesity. Micro RNA s are emerging as key regulators in development and disease. Combining micro RNA 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 BMP 7. 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 AMPK α1 by targeting HIF 1an, 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 micro RNA ‐regulated signaling network that controls brown adipogenesis and may be a potential therapeutic target for human metabolic disorders.