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

被引：190

作者：

Boergeson, Emma ^{[1
,2
,3
]}

Johnson, Andrew M. F. ^{[4
]}

Lee, Yun Sok ^{[4
]}

Till, Andreas ^{[5
,6
,7
]}

Syed, Gulam Hussain ^{[8
]}

Ali-Shah, Syed Tasadaque ^{[9
]}

Guiry, Patrick J. ^{[9
]}

Dalli, Jesmond ^{[10
,11
]}

Colas, Romain A. ^{[10
,11
]}

Serhan, Charles N. ^{[10
,11
]}

Sharma, Kumar ^{[1
,2
]}

Godson, Catherine ^{[3
]}

机构：

[1] Univ Calif San Diego, Dept Med, Inst Metab Med, Ctr Renal Translat Med,Div Nephrol Hypertens, La Jolla, CA 92093 USA

[2] San Diego Healthcare Syst, Vet Affair, Vet Med Res Fdn, La Jolla, CA 92093 USA

[3] Univ Coll Dublin, UCD Conway Inst, Diabet Complicat Res Ctr, Sch Med, Dublin 4, Ireland

[4] Univ Calif San Diego, Dept Med, Div Endocrinol & Metab, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

[6] Univ Calif San Diego, San Diego Ctr Syst Biol, La Jolla, CA 92093 USA

[7] Univ Clin Bonn, Inst Reconstruct Neurobiol, LIFE&BRAIN, D-53127 Bonn, Germany

[8] Univ Calif San Diego, Dept Med, Div Infect Dis, La Jolla, CA 92093 USA

[9] Univ Coll Dublin, UCD Conway Inst, UCD Sch Chem, Ctr Synth & Chem Biol, Dublin 4, Ireland

[10] Brigham & Womens Hosp, Dept Anesthesiol Perioperat & Pain Med, Ctr Expt Therapeut & Reperfus Injury, Harvard Inst Med, Boston, MA 02115 USA

[11] Harvard Univ, Sch Med, Boston, MA 02115 USA

来源：

CELL METABOLISM | 2015年 / 22卷 / 01期

基金：

爱尔兰科学基金会;

关键词：

PRORESOLVING LIPID MEDIATORS; RESOLVIN D1; MACROPHAGE POLARIZATION; INSULIN SENSITIVITY; HUMAN PHAGOCYTES; ANNEXIN A1; TISSUE; RESOLUTION; ADIPONECTIN; AUTOPHAGY;

D O I：

10.1016/j.cmet.2015.05.003

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The role of inflammation in obesity-related pathologies is well established. We investigated the therapeutic potential of LipoxinA(4) (LXA(4): 5(S), 6(R), 15(S)-trihydroxy-7E, 9E, 11Z, 13E,-eicosatetraenoic acid) and a synthetic 15(R)-Benzo-LXA(4)-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, LXA(4) reduced liver weight, serum alanine-aminotransferase, and hepatic triglycerides. LXA(4) decreased obesity-induced adipose inflammation, attenuating TNF-alpha and CD11c(+) M1-macrophages (M Phi s), while restoring CD206(+) M2-M Phi s and increasing Annexin-A1. LXs did not affect renal or hepatic M Phi s, 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.

引用

页码：125 / 137

页数：13

共 59 条

[11] Metabolic remodeling of white adipose tissue in obesity [J].