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

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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

Fingerprint

Kidney Diseases
Lipoxins
Liver Diseases
Obesity
Inflammation
Macrophages
Pathology
Chronic Renal Insufficiency
Liver
Annexin A1
Arachidonic Acids
Glucose Intolerance
Adiponectin
Autophagy
High Fat Diet
Fatty Liver
lipoxin A4
Alanine Transaminase
Triglycerides
Fats

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cell Biology

Cite this

Börgeson, E., Johnson, A. M. F., Lee, Y. S., Till, A., Syed, G. H., Ali-Shah, S. T., ... 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

Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. / Börgeson, Emma; Johnson, Andrew M.F.; Lee, Yun Sok; Till, Andreas; Syed, Gulam Hussain; Ali-Shah, Syed Tasadaque; Guiry, Patrick J.; Dalli, Jesmond; Colas, Romain A.; Serhan, Charles N.; Sharma, Kumar; Godson, Catherine.

In: Cell Metabolism, Vol. 22, No. 1, 01.01.2015, p. 125-137.

Research output: Contribution to journalArticle

Börgeson, E, Johnson, AMF, Lee, YS, Till, A, Syed, GH, Ali-Shah, ST, Guiry, PJ, Dalli, J, Colas, RA, Serhan, CN, Sharma, K & Godson, C 2015, 'Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease', Cell Metabolism, vol. 22, no. 1, pp. 125-137. https://doi.org/10.1016/j.cmet.2015.05.003
Börgeson, Emma ; Johnson, Andrew M.F. ; Lee, Yun Sok ; Till, Andreas ; Syed, Gulam Hussain ; Ali-Shah, Syed Tasadaque ; Guiry, Patrick J. ; Dalli, Jesmond ; Colas, Romain A. ; Serhan, Charles N. ; Sharma, Kumar ; Godson, Catherine. / Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. In: Cell Metabolism. 2015 ; Vol. 22, No. 1. pp. 125-137.
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