Steen Bønløkke Pedersen

Beta-1 and not beta-3-adrenergic receptors may be the primary regulator of human brown adipocyte metabolism

Publikation: Bidrag til tidsskrift/Konferencebidrag i tidsskrift /Bidrag til avisTidsskriftartikelForskningpeer review

DOI

  • Mette Ji Riis-Vestergaard
  • ,
  • Bjørn Richelsen
  • Jens Meldgaard Bruun
  • Wei Li, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 15, DK-2100 København Ø, Denmark
  • ,
  • Jacob B Hansen, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 15, DK-2100 København Ø, Denmark
  • ,
  • Steen Bønløkke Pedersen

PURPOSE: Brown adipose tissue (BAT) activation in humans has gained interest as a potential target for treatment of obesity and insulin resistance. In rodents, BAT is primarily induced through beta-3-adrenergic receptor (ADRB3) stimulation, whereas the primary beta-adrenergic receptors (ADRBs) involved in human BAT activation are debated. We evaluated the importance of different ADRB subtypes for uncoupling protein 1 (UCP1) induction in human brown adipocytes.

METHODS: A human BAT cell model (TERT-hBA) was investigated for subtype-specific ADRB agonists and receptor knock down on UCP1 mRNA levels and lipolysis (glycerol release). In addition, fresh human BAT biopsies and TERT-hBA were evaluated for expression of ADRB1, ADRB2 and ADRB3 using RT-qPCR.

RESULTS: The predominant ADRB subtype in TERT-hBA adipocytes and BAT biopsies was ADRB1. In TERT-hBA, UCP1 mRNA expression was stimulated 11.0-fold by dibutyryl cAMP (dbcAMP), 8.0-8.4-fold by isoproterenol (ISO; a pan-ADRB agonist) and 6.1-12.7-fold by dobutamine (ADRB1 agonist) whereas neither procaterol (ADRB2 agonist), CL314.432 or Mirabegron (ADRB3 agonists) affected UCP1. Similarly, dbcAMP, ISO and dobutamine stimulated glycerol release, whereas lipolysis was unaffected by ADRB2 and ADRB3 agonists. Selective knock down of ADRB1 significantly attenuated ISO-induced UCP1 expression.

CONCLUSIONS: The adrenergic stimulation of UCP1 and lipolysis may mainly be mediated through ADRB1. Moreover, ADRB1 is the predominant ADRB in both TERT-hBA and human BAT biopsies. Thus, UCP1 expression in human BAT may, unlike in rodents, primarily be regulated by ADRB1. These findings may have implications for ADRB agonists as future therapeutic compounds for human BAT activation.

OriginalsprogEngelsk
Artikelnummerdgz298
TidsskriftThe Journal of clinical endocrinology and metabolism
Vol/bind105
Nummer4
ISSN0021-972X
DOI
StatusUdgivet - 2020

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