HuR expression in adipose tissue mediates energy expenditure and acute thermogenesis independent of UCP1 expression

HuR expression in adipose tissue mediates energy expenditure and acute thermogenesis independent of UCP1 expression

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...

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Bibliographic Details
Main Authors: Sarah R. Anthony, Adrienne Guarnieri, Lindsey Lanzillotta, Anamarie Gozdiff, Lisa C. Green, Katherine O’Grady, Robert N. Helsley, A. Phillip Owens, Michael Tranter
Format: Article
Language:English
Published: Taylor & Francis Group 2020-01-01
Series:Adipocyte
Subjects:
hur
adipose tissue
brown fat
thermogenesis
ucp1
gene expression
calcium transport
Online Access:http://dx.doi.org/10.1080/21623945.2020.1782021
Description
Summary: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
ISSN:2162-3945
2162-397X

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