Login / Signup

ADRA1A-Gα q signalling potentiates adipocyte thermogenesis through CKB and TNAP.

Janane F RahbaniCharlotte ScholtesDamien M LagardeMohammed F HussainAnna RoeslerChristien B DykstraJakub BunkBozena SamborskaShannon L O'BrienEmma TrippAlain PacisAnthony R AngueiraOlivia S JohansenJessica CinkornpuminIshtiaque HossainMatthew D LynesYang ZhangAndrew P WhiteWilliam A PastorMaria ChondronikolaLabros SidossisSamuel KleinAnastasia KralliAaron M CypessSteen Bønlykke PedersenNiels JessenYu-Hua TsengZachary Gerhart-HinesPatrick SealeDavide CalebiroVincent GiguèreLawrence Kazak
Published in: Nature metabolism (2022)
Noradrenaline (NA) regulates cold-stimulated adipocyte thermogenesis 1 . Aside from cAMP signalling downstream of β-adrenergic receptor activation, how NA promotes thermogenic output is still not fully understood. Here, we show that coordinated α 1 -adrenergic receptor (AR) and β 3 -AR signalling induces the expression of thermogenic genes of the futile creatine cycle 2,3 , and that early B cell factors, oestrogen-related receptors and PGC1α are required for this response in vivo. NA triggers physical and functional coupling between the α 1 -AR subtype (ADRA1A) and Gα q to promote adipocyte thermogenesis in a manner that is dependent on the effector proteins of the futile creatine cycle, creatine kinase B and tissue-non-specific alkaline phosphatase. Combined Gα q and Gα s signalling selectively in adipocytes promotes a continual rise in whole-body energy expenditure, and creatine kinase B is required for this effect. Thus, the ADRA1A-Gα q -futile creatine cycle axis is a key regulator of facultative and adaptive thermogenesis.
Keyphrases
  • adipose tissue
  • insulin resistance
  • binding protein
  • protein kinase
  • poor prognosis
  • physical activity
  • skeletal muscle
  • tyrosine kinase
  • metabolic syndrome
  • gene expression
  • type iii