Article (Scientific journals)
The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites
Bean, Camilla; Audano, A; Varanita, tatianna et al.
2021In Nature Metabolism
Peer reviewed
 

Files


Full Text
bean et al.pdf
Author preprint (3.47 MB)
Request a copy

All documents in ORBi are protected by a user license.

Send to



Details



Abstract :
[en] White to brown/beige adipocytes conversion is a possible therapeutic strategy to tackle the current obesity epidemics. While mitochondria are key for energy dissipation in brown fat, it is unknown if they can drive adipocyte browning. Here, we show that the mitochondrial cristae biogenesis protein optic atrophy 1 (Opa1) facilitates cell-autonomous adipocyte browning. In two cohorts of patients with obesity, including weight discordant monozygotic twin pairs, adipose tissue OPA1 levels are reduced. In the mouse, Opa1 overexpression favours white adipose tissue expandability as well as browning, ultimately improving glucose tolerance and insulin sensitivity. Transcriptomics and metabolomics analyses identify the Jumanji family chromatin remodelling protein Kdm3a and urea cycle metabolites, including fumarate, as effectors of Opa1-dependent browning. Mechanistically, the higher cyclic adenosine monophosphate (cAMP) levels in Opa1 pre-adipocytes activate cAMP-responsive element binding protein (CREB), which transcribes urea cycle enzymes. Flux analyses in pre-adipocytes indicate that Opa1-dependent fumarate accumulation depends on the urea cycle. Conversely, adipocyte-specific Opa1 deletion curtails urea cycle and beige differentiation of pre-adipocytes, and is rescued by fumarate supplementation. Thus, the urea cycle links the mitochondrial dynamics protein Opa1 to white adipocyte browning.
Disciplines :
Biochemistry, biophysics & molecular biology
Author, co-author :
Bean, Camilla
Audano, A
Varanita, tatianna
Favaretto, F
Medaglia, marta
Gerdol, M
Pernas, L
Giacomello, Marta
Herkenne, Stéphanie  ;  Université de Liège - ULiège > GIGA Cancer - Molecular Angiogenesis Laboratory
Muniandy, M
Heinonen, S
Milan, G
Pallavicini, A
Pietiläinen, KH
Vettor, R
Mitro, N
Scorrano, Luca
More authors (7 more) Less
Language :
English
Title :
The mitochondrial protein Opa1 promotes adipocyte browning that is dependent on urea cycle metabolites
Publication date :
03 December 2021
Journal title :
Nature Metabolism
eISSN :
2522-5812
Peer reviewed :
Peer reviewed
Available on ORBi :
since 13 January 2022

Statistics


Number of views
75 (3 by ULiège)
Number of downloads
2 (2 by ULiège)

Scopus citations®
 
40
Scopus citations®
without self-citations
35
OpenCitations
 
8

Bibliography


Similar publications



Contact ORBi