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

Cell Metab. 2015 Jul 7;22(1):125-37. doi: 10.1016/j.cmet.2015.05.003. Epub 2015 Jun 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Adipose Tissue / drug effects
  • Adipose Tissue / immunology
  • Adipose Tissue / pathology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / therapeutic use*
  • Autophagy / drug effects
  • Inflammation / complications*
  • Inflammation / drug therapy*
  • Inflammation / immunology
  • Inflammation / pathology
  • Kidney / drug effects
  • Kidney / immunology
  • Kidney / pathology
  • Kidney Diseases / complications*
  • Kidney Diseases / drug therapy
  • Kidney Diseases / immunology
  • Kidney Diseases / pathology
  • Lipoxins / therapeutic use*
  • Liver / drug effects
  • Liver / immunology
  • Liver / pathology
  • Liver Diseases / complications*
  • Liver Diseases / drug therapy
  • Liver Diseases / immunology
  • Liver Diseases / pathology
  • Mice, Inbred C57BL
  • Obesity / complications*
  • Obesity / immunology


  • Anti-Inflammatory Agents, Non-Steroidal
  • Lipoxins
  • lipoxin A4