Forskning
Udskriv Udskriv
Switch language
Region Hovedstaden - en del af Københavns Universitetshospital
Udgivet

Human Brown Adipocyte Thermogenesis Is Driven by β2-AR Stimulation

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

DOI

  1. FGF21 suppresses alcohol consumption through an amygdalo-striatal circuit

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Human skeletal muscle CD90+ fibro-adipogenic progenitors are associated with muscle degeneration in type 2 diabetic patients

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Voices: Insulin and beyond

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. A cell-autonomous signature of dysregulated protein phosphorylation underlies muscle insulin resistance in type 2 diabetes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. Proteomics-Based Comparative Mapping of the Secretomes of Human Brown and White Adipocytes Reveals EPDR1 as a Novel Batokine

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  1. Can we target obesity using a single-cell atlas of adipose tissue?

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  2. Isolation and Characterization of Human Brown Adipocytes

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  3. Altered brown fat thermoregulation and enhanced cold-induced thermogenesis in young, healthy, winter-swimming men

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  4. Lipolysis drives expression of the constitutively active receptor GPR3 to induce adipose thermogenesis

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

  5. VPS39-deficiency observed in type 2 diabetes impairs muscle stem cell differentiation via altered autophagy and epigenetics

    Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Vis graf over relationer

Stimulation of brown adipose tissue (BAT) thermogenesis in humans has emerged as an attractive target to improve metabolic health. Pharmacological stimulations targeting the β 3-adrenergic receptor (β 3-AR), the adrenergic receptor believed to mediate BAT thermogenesis, have historically performed poorly in human clinical trials. Here we report that, in contrast to rodents, human BAT thermogenesis is not mediated by the stimulation of β 3-AR. Oral administration of the β 3-AR agonist mirabegron only elicited increases in BAT thermogenesis when ingested at the maximal allowable dose. This led to off-target binding to β 1-AR and β 2-AR, thereby increasing cardiovascular responses and white adipose tissue lipolysis, respectively. ADRB2 was co-expressed with UCP1 in human brown adipocytes. Pharmacological stimulation and inhibition of the β 2-AR as well as knockdown of ADRB1, ADRB2, or ADRB3 in human brown adipocytes all confirmed that BAT lipolysis and thermogenesis occur through β 2-AR signaling in humans (ClinicalTrials.gov NCT02811289). Blondin et al. reveal that therapeutic doses of the β 3-AR agonist mirabegron do not stimulate human BAT. Biopsies from participants show that the lack of effect may be explained by the absence of β 3-AR and primary expression of β 2-AR. In human brown adipocytes, β 2-AR agonism increases respiration, whereas pharmacological and genetic inhibition of β 2-AR decrease respiration.

OriginalsprogEngelsk
TidsskriftCell Metabolism
Vol/bind32
Udgave nummer2
Sider (fra-til)287-300.e7
ISSN1550-4131
DOI
StatusUdgivet - 4 aug. 2020

Bibliografisk note

Copyright © 2020 Elsevier Inc. All rights reserved.

ID: 60805730