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HuR expression in adipose tissue mediates energy expenditure and acute
thermogenesis independent of UCP1 expression.
Authors Anthony SR, Guarnieri A, Lanzillotta L, Gozdiff A, Green LC, O'Grady K, Helsley
RN, Owens Iii AP, Tranter M
Submitted By Submitted Externally on 9/28/2020
Status Published
Journal Adipocyte
Year 2020
Date Published 12/1/2020
Volume : Pages 9 : 335 - 345
PubMed Reference 32713230
Abstract The goal of this study was to define the functional role of adipocyte-specific
expression of the RNA binding protein Human antigen R (HuR). Mice with an
adipocyte-specific deletion of HuR (Adipo-HuR-/- ) were generated by crossing
HuR floxed (HuRfl/fl ) mice with mice expressing adiponectin-driven
cre-recombinase (Adipoq-cre). Our results show that Adipo-HuR-/- mice display a
lean phenotype compared to wild-type littermate controls. HuR deletion results
in a diet-independent reduction in percent body fat composition along with an
increase in energy expenditure. Functionally, Adipo-HuR-/- mice show a
significant impairment in acute adaptive thermogenesis (six hours at 4°C), but
uncoupling protein 1 (UCP1) protein expression in brown adipose tissue (BAT) is
unchanged compared to control. Pharmacological inhibition of HuR also results in
a marked decline in core body temperature following acute cold challenge
independent of UCP1 protein expression. Among the 588 HuR-dependent genes in BAT
identified by RNA-seq analysis, gene ontology analysis shows a significant
enrichment in mediators of calcium transport and signalling, almost all of which
are decreased in Adipo-HuR-/- mice compared to control. In conclusion, adipocyte
expression of HuR plays a central role in metabolic homoeostasis and mediates
UCP1-independent thermogenesis in BAT, potentially through post-transcriptional
control of intracellular calcium transport.Abbreviations: Adipo-HuR-/-:
Adipocyte-specific HuR deletion mice; BAT: Brown adipose tissue; HuR: Human
antigen R; UCP1: Uncoupling protein 1.


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