RT Journal Article
T1 Accelerated phosphatidylcholine turnover in macrophages promotes adipose tissue inflammation in obesity.
A1 Petkevicius, Kasparas
A1 Virtue, Sam
A1 Bidault, Guillaume
A1 Jenkins, Benjamin
A1 Çubuk, Cankut
A1 Morgantini, Cecilia
A1 Aouadi, Myriam
A1 Dopazo, Joaquin
A1 Serlie, Mireille J
A1 Koulman, Albert
A1 Vidal-Puig, Antonio
K1 ER stress
K1 adipose tissue
K1 cell biology
K1 fatty acid
K1 human
K1 human biology
K1 immunometabolism
K1 macrophage
K1 medicine
K1 membrane lipid
K1 mouse
AB 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.
YR 2019
FD 2019-08-16
LK http://hdl.handle.net/10668/14401
UL http://hdl.handle.net/10668/14401
LA en
DS RISalud
RD Apr 11, 2025