Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism
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Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism. / Riis-Vestergaard, Mette Ji; Richelsen, Bjørn; Bruun, Jens Meldgaard; Li, Wei; Hansen, Jacob B.; Pedersen, Steen Bønløkke.
In: The Journal of clinical endocrinology and metabolism, Vol. 105, No. 4, dgz298, 2020.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Beta-1 and Not Beta-3 Adrenergic Receptors May Be the Primary Regulator of Human Brown Adipocyte Metabolism
AU - Riis-Vestergaard, Mette Ji
AU - Richelsen, Bjørn
AU - Bruun, Jens Meldgaard
AU - Li, Wei
AU - Hansen, Jacob B.
AU - Pedersen, Steen Bønløkke
PY - 2020
Y1 - 2020
N2 - 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 knockdown 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-fold to 8.4-fold by isoproterenol (ISO; a pan-ADRB agonist), and 6.1-fold to 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 knockdown of ADRB1 significantly attenuated ISO-induced UCP1 expression. CONCLUSION: 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.
AB - 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 knockdown 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-fold to 8.4-fold by isoproterenol (ISO; a pan-ADRB agonist), and 6.1-fold to 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 knockdown of ADRB1 significantly attenuated ISO-induced UCP1 expression. CONCLUSION: 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.
KW - beta adrenergic regulation
KW - beta-3 adrenergic receptor
KW - brown adipocytes
KW - human
KW - UCP1
U2 - 10.1210/clinem/dgz298
DO - 10.1210/clinem/dgz298
M3 - Journal article
C2 - 31867674
VL - 105
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
SN - 0021-972X
IS - 4
M1 - dgz298
ER -
ID: 239861204