| Literature DB >> 26052006 |
Emma Börgeson1, Andrew M F Johnson2, Yun Sok Lee2, Andreas Till3, Gulam Hussain Syed4, Syed Tasadaque Ali-Shah5, Patrick J Guiry5, Jesmond Dalli6, Romain A Colas6, Charles N Serhan6, Kumar Sharma7, Catherine Godson8.
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-α and CD11c(+) M1-macrophages (MΦs), while restoring CD206(+) M2-MΦs and increasing Annexin-A1. LXs did not affect renal or hepatic MΦs, 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.Entities:
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Year: 2015 PMID： 26052006 PMCID： PMC4584026 DOI： 10.1016/j.cmet.2015.05.003
Source DB: PubMed Journal: Cell Metab ISSN： 1550-4131 Impact factor: 27.287