Copperi 2022 Commun Biol

From Bioblast
Publications in the MiPMap
Copperi F, Schleis I, Roumain M, Muccioli GG, Casola S, Klingenspor M, Pfeifer A, Gnad T (2022) EBI2 is a negative modulator of brown adipose tissue energy expenditure in mice and human brown adipocytes.

Β» Commun Biol 5:280. PMID: 35351968 Open Access

Copperi Francesca,  Schleis Inna,  Roumain Martin, Muccioli Giulio G,  Casola Stefano,  Klingenspor Martin,  Pfeifer Alexander,  Gnad Thorsten (2022) Commun Biol

Abstract: Pharmacological activation of brown adipose tissue (BAT) is an attractive approach for increasing energy expenditure to counteract obesity. Given the side-effects of known activators of BAT, we studied inhibitors of BAT as a novel, alternative concept to regulate energy expenditure. We focused on G-protein-coupled receptors that are one of the major targets of clinically used drugs. Here, we identify GPR183, also known as EBI2, as the most highly expressed inhibitory G-protein-coupled receptor in BAT among the receptors examined. Activation of EBI2 using its endogenous ligand 7Ξ±,25-dihydroxycholesterol significantly decreases BAT-mediated energy expenditure in mice. In contrast, mice deficient for EBI2 show increased energy dissipation in response to cold. Interestingly, only thermogenic adipose tissue depots - BAT and subcutaneous white adipose tissue -respond to 7Ξ±,25-dihydroxycholesterol treatment/EBI2 activation but not gonadal white fat, which has the lowest thermogenic capacity. EBI2 activation in brown adipocytes significantly reduces norepinephrine-induced cAMP production, whereas pharmacological inhibition or genetic ablation of EBI2 results in an increased response. Importantly, EBI2 significantly inhibits norepinephrine-induced activation of human brown adipocytes. Our data identify the 7Ξ±,25-dihydroxycholesterol/EBI2 signaling pathway as a so far unknown BAT inhibitor. Understanding the inhibitory regulation of BAT might lead to novel pharmacological approaches to increase the activity of thermogenic adipose tissue and whole body energy expenditure in humans.

β€’ Bioblast editor: Plangger M β€’ O2k-Network Lab: DE Freising Klingenspor M, DE Bonn Pfeifer A

Labels: MiParea: Respiration  Pathology: Obesity 

Organism: Mouse  Tissue;cell: Fat  Preparation: Intact cells 

Coupling state: LEAK, OXPHOS, ET  Pathway:HRR: Oxygraph-2k 


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