| 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.
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