Adipocyte (Jan 2020)

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

  • Sarah R. Anthony,
  • Adrienne Guarnieri,
  • Lindsey Lanzillotta,
  • Anamarie Gozdiff,
  • Lisa C. Green,
  • Katherine O’Grady,
  • Robert N. Helsley,
  • A. Phillip Owens,
  • Michael Tranter

DOI
https://doi.org/10.1080/21623945.2020.1782021
Journal volume & issue
Vol. 9, no. 1
pp. 336 – 346

Abstract

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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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