Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease

Emma Börgeson, Andrew M.F. Johnson, Yun Sok Lee, Andreas Till, Gulam Hussain Syed, Syed Tasadaque Ali-Shah, Patrick J. Guiry, Jesmond Dalli, Romain A. Colas, Charles N. Serhan, Kumar Sharma, Catherine Godson

Research output: Contribution to journalArticle

84 Scopus citations

Abstract

Summary 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.

Original languageEnglish (US)
Pages (from-to)125-137
Number of pages13
JournalCell Metabolism
Volume22
Issue number1
DOIs
StatePublished - Jan 1 2015
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

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    Börgeson, E., Johnson, A. M. F., Lee, Y. S., Till, A., Syed, G. H., Ali-Shah, S. T., Guiry, P. J., Dalli, J., Colas, R. A., Serhan, C. N., Sharma, K., & Godson, C. (2015). Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. Cell Metabolism, 22(1), 125-137. https://doi.org/10.1016/j.cmet.2015.05.003