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

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

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.

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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