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

Overview

Journal Cell Metab

Publisher Cell Press

Specialties Cell Biology
Endocrinology

Date 2015 Jun 9

PMID 26052006

Citations 97

Authors

Emma Borgeson

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

Affiliations

Soon will be listed here.

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.

Citing Articles

Attenuation of adipose tissue inflammation by pro-resolving lipid mediators.

Clark M, Suur B, Sotak M, Borgeson E Curr Opin Endocr Metab Res. 2024; 36:100539.

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Lipoxin A improves cardiac remodeling and function in diabetes-associated cardiac dysfunction.

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