| First Author | Börgeson E | Year | 2015 |
| Journal | Cell Metab | Volume | 22 |
| Issue | 1 | Pages | 125-37 |
| PubMed ID | 26052006 | Mgi Jnum | J:299575 |
| Mgi Id | MGI:6501242 | Doi | 10.1016/j.cmet.2015.05.003 |
| Citation | Borgeson E, et al. (2015) Lipoxin A4 Attenuates Obesity-Induced Adipose Inflammation and Associated Liver and Kidney Disease. Cell Metab 22(1):125-37 |
| abstractText | 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-alpha and CD11c(+) M1-macrophages (MPhis), while restoring CD206(+) M2-MPhis and increasing Annexin-A1. LXs did not affect renal or hepatic MPhis, 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. |
