Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver
and Kidney Disease.
Authors Börgeson E, Johnson AM, Lee YS, Till A, Syed GH, Ali-Shah ST, Guiry PJ, Dalli J,
Colas RA, Serhan CN, Sharma K, Godson C
Submitted By Catherine Godson on 6/9/2015
Status Published
Journal Cell Metabolism
Year 2015
Date Published 6/3/2015
Volume : Pages Not Specified : Not Specified
PubMed Reference 26052006
Abstract The role of inflammation in obesity-related pathologies is well established. We
investigated the therapeutic potential of LipoxinA4
(LXA4:5(S),6(R),15(S)-trihydroxy-7E,9E,11Z,13E,-eicosatetraenoic acid) and a
synthetic 15(R)-Benzo-LXA4-analog as interventions in a 3-month high-fat diet
(HFD; 60% fat)-induced obesity model. Obesity caused distinct pathologies,
including impaired glucose tolerance, adipose inflammation, fatty liver, and
chronic kidney disease (CKD). Lipoxins (LXs) attenuated obesity-induced CKD,
reducing glomerular expansion, mesangial matrix, and urinary H2O2. Furthermore,
LXA4 reduced liver weight, serum alanine-aminotransferase, and hepatic
triglycerides. LXA4 decreased obesity-induced adipose inflammation, attenuating
TNF-a and CD11c(+) M1-macrophages (MFs), while restoring CD206(+) M2-MFs and
increasing Annexin-A1. LXs did not affect renal or hepatic MFs, suggesting
protection occurred via attenuation of adipose inflammation. LXs restored
adipose expression of autophagy markers LC3-II and p62. LX-mediated protection
was demonstrable in adiponectin(-/-) mice, suggesting that the mechanism was
adiponectin independent. In conclusion, LXs protect against obesity-induced
systemic disease, and these data support a novel therapeutic paradigm for
treating obesity and associated pathologies.

Investigators with authorship
Catherine GodsonUniversity College Dublin
Kumar SharmaUniversity of California San Diego