miRNA-32 Drives Brown Fat Thermogenesis and Trans-activates Subcutaneous White Fat Browning in Mice

Cell Reports
Raymond NgFeng Xu

Abstract

Brown adipose tissue (BAT) activation and subcutaneous white fat browning are essential components of the thermogenic response to cold stimulus in mammals. microRNAs have been shown to regulate both processes in cis. Here, we identify miR-32 as a BAT-specific super-enhancer-associated miRNA in mice that is selectively expressed in BAT and further upregulated during cold exposure. Inhibiting miR-32 in vivo led to impaired cold tolerance, decreased BAT thermogenesis, and compromised white fat browning as a result of reduced serum FGF21 levels. Further examination showed that miR-32 directly represses its target gene Tob1, thereby activating p38 MAP kinase signaling to drive FGF21 expression and secretion from BAT. BAT-specific miR-32 overexpression led to increased BAT thermogenesis and serum FGF21 levels, which further promotes white fat browning in trans. Our results suggested miR-32 and Tob1 as modulators of FGF21 signaling that can be manipulated for therapeutic benefit against obesity and metabolic syndrome.

Citations

Jan 31, 2019·Journal of Cellular Physiology·Yunyun JinXianyong Lan
Apr 13, 2020·Mammalian Genome : Official Journal of the International Mammalian Genome Society·Meriem Ouni, Annette Schürmann
Aug 5, 2020·RNA Biology·Juanhong Liu, Feng Liu
Sep 8, 2017·Frontiers in Endocrinology·Farnaz ShamsiYu-Hua Tseng
Aug 25, 2018·Journal of Internal Medicine·S DadvarJ L Ruas
May 24, 2019·Frontiers in Genetics·Hongxiao JiaoWei-Dong Li
Aug 12, 2018·International Journal of Molecular Sciences·Chong XueJingyuan Chen
Dec 7, 2018·Journal of Physiology and Biochemistry·A Kaisanlahti, T Glumoff
Jun 20, 2018·International Journal of Molecular Sciences·Xu PengFeng Xu
Dec 1, 2020·Frontiers in Cell and Developmental Biology·Jin QiuLingyan Xu
Jan 29, 2021·Nature Reviews. Molecular Cell Biology·Begoña Canovas, Angel R Nebreda
Nov 20, 2020·Cells·Seley GharaneiHarpal S Randeva
Feb 13, 2021·Molecular Therapy. Methods & Clinical Development·Nicholas J QueenLei Cao
Mar 5, 2021·Arteriosclerosis, Thrombosis, and Vascular Biology·Milessa Silva AfonsoKathryn J Moore
Jul 22, 2021·Journal of Molecular Cell Biology·Wei GaoQin Yang

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Datasets Mentioned

BETA
GSM822520

Methods Mentioned

BETA
immunoprecipitation
ChIP-seq
ELISAs
transfections
transfection
Assay
PCR
profiler

Software Mentioned

makeBigWig
ImageJ
Wash U Epigenetics browser
IHC profiler Plugin ImageJ
bowtie
ROSE
CDS
BigWig
makeTagDirectory
DIANA

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