Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity.
ER stress
adipose tissue
cell biology
fatty acid
human
human biology
immunometabolism
macrophage
medicine
membrane lipid
mouse
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
16 08 2019
16 08 2019
Historique:
received:
26
04
2019
accepted:
15
08
2019
pubmed:
17
8
2019
medline:
15
2
2020
entrez:
17
8
2019
Statut:
epublish
Résumé
White adipose tissue (WAT) inflammation contributes to the development of insulin resistance in obesity. While the role of adipose tissue macrophage (ATM) pro-inflammatory signalling in the development of insulin resistance has been established, it is less clear how WAT inflammation is initiated. Here, we show that ATMs isolated from obese mice and humans exhibit markers of increased rate of de novo phosphatidylcholine (PC) biosynthesis. Macrophage-specific knockout of phosphocholine cytidylyltransferase A (CCTα), the rate-limiting enzyme of de novo PC biosynthesis pathway, alleviated obesity-induced WAT inflammation and insulin resistance. Mechanistically, CCTα-deficient macrophages showed reduced ER stress and inflammation in response to palmitate. Surprisingly, this was not due to lower exogenous palmitate incorporation into cellular PCs. Instead, CCTα-null macrophages had lower membrane PC turnover, leading to elevated membrane polyunsaturated fatty acid levels that negated the pro-inflammatory effects of palmitate. Our results reveal a causal link between obesity-associated increase in de novo PC synthesis, accelerated PC turnover and pro-inflammatory activation of ATMs.
Identifiants
pubmed: 31418690
doi: 10.7554/eLife.47990
pii: 47990
pmc: PMC6748830
doi:
pii:
Substances chimiques
Phosphatidylcholines
0
Choline-Phosphate Cytidylyltransferase
EC 2.7.7.15
Banques de données
GEO
['GSE36669']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : British Heart Foundation
ID : RG/12/13/29853
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_G0802535
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12012/5
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0600717
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_00014/2
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC_MC_UU_12012/2
Pays : United Kingdom
Organisme : Wellcome Trust
ID : Strategic Award
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0802051
Pays : United Kingdom
Organisme : British Heart Foundation
ID : Programme Grant RG/18/7/33636
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 4-year PhD programme in Metabolic and Cardiovascular Disease (102354/Z/13/Z)
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400192
Pays : United Kingdom
Organisme : Medical Research Council
ID : MRC_MC_UU_12012/5
Pays : United Kingdom
Informations de copyright
© 2019, Petkevicius et al.
Déclaration de conflit d'intérêts
KP, SV, GB, BJ, CÇ, CM, MA, JD, MS, AK, AV No competing interests declared
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