Lipoxin A4 attenuates adipose inflammation

被引:89
作者
Boergeson, Emma [1 ]
McGillicuddy, Fiona C. [2 ,3 ]
Harford, Karen A. [2 ,3 ]
Corrigan, Niamh [1 ]
Higgins, Debra F. [1 ]
Maderna, Paola [1 ]
Roche, Helen M. [2 ,3 ]
Godson, Catherine [1 ]
机构
[1] Univ Coll Dublin, Diabet Res Ctr, Conway Inst, Sch Med & Med Sci, Dublin 2, Ireland
[2] Univ Coll Dublin, Nutrigen Res Grp, Conway Inst, Dublin 2, Ireland
[3] Univ Coll Dublin, Sch Publ Hlth, Dublin 2, Ireland
基金
爱尔兰科学基金会;
关键词
resolution; proresolving eicosanoids; obesity; insulin resistance; NECROSIS-FACTOR-ALPHA; MACROPHAGE ACCUMULATION; APOPTOTIC NEUTROPHILS; INSULIN SENSITIVITY; TISSUE MACROPHAGES; LINOLEIC-ACID; CUTTING EDGE; BONE-MARROW; RESOLVIN D1; IN-VITRO;
D O I
10.1096/fj.12-208249
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Aging and adiposity are associated with chronic low-grade inflammation, which underlies the development of obesity-associated complications, including type 2 diabetes mellitus (T2DM). The mechanisms underlying adipose inflammation may include macrophage infiltration and activation, which, in turn, affect insulin sensitivity of adipocytes. There is a growing appreciation that specific lipid mediators (including lipoxins, resolvins, and protectins) can promote the resolution of inflammation. Here, we investigated the effect of lipoxin A(4) (LXA(4)), the predominant endogenously generated lipoxin, on adipose tissue inflammation. Using adipose tissue explants from perigonadal depots of aging female C57BL/6J mice (Animalia, Chordata, Mus musculus) as a model of age-associated adipose inflammation, we report that LXA(4) (1 nM) attenuates adipose inflammation, decreasing IL-6 and increasing IL-10 expression (P<0.05). The altered cytokine milieu correlated with increased GLUT-4 and IRS-1 expression, suggesting improved insulin sensitivity. Further investigations revealed the ability of LXA(4) to rescue macrophage-induced desensitization to insulin-stimulated signaling and glucose uptake in cultured adipocytes, using vehicle-stimulated cells as controls. This was associated with preservation of Akt activation and reduced secretion of proinflammatory cytokines, including TNF-alpha. We therefore propose that LXA(4) may represent a potentially useful and novel therapeutic strategy to subvert adipose inflammation and insulin resistance, key components of T2DM.-Borgeson, E., McGillicuddy, F. C., Harford, K. A., Corrigan, N., Higgins, D. F., Maderna, P., Roche, H. M., Godson C. Lipoxin A(4) attenuates adipose inflammation. FASEB J. 26, 4287-4294 (2012). www.fasebj.org
引用
收藏
页码:4287 / 4294
页数:8
相关论文
共 67 条
[11]   Lipoxin A4 inhibits IL-1β-induced IL-8 and ICAM-1 expression in 1321N1 human astrocytoma cells [J].
Decker, Yann ;
McBean, Gethin ;
Godson, Catherine .
AMERICAN JOURNAL OF PHYSIOLOGY-CELL PHYSIOLOGY, 2009, 296 (06) :C1420-C1427
[12]   Type 2 diabetes as an inflammatory disease [J].
Donath, Marc Y. ;
Shoelson, Steven E. .
NATURE REVIEWS IMMUNOLOGY, 2011, 11 (02) :98-107
[13]   Image-based high-throughput quantification of cellular fat accumulation [J].
Dragunow, Mike ;
Cameron, Rachel ;
Narayan, Pritika ;
O'Carroll, Simon .
JOURNAL OF BIOMOLECULAR SCREENING, 2007, 12 (07) :999-1005
[14]   Aging is characterized by a profound reduction in anti-inflammatory lipoxin A4 levels [J].
Gangemi, S ;
Pescara, L ;
D'Urbano, E ;
Basile, G ;
Nicita-Mauro, V ;
Davì, G ;
Romano, M .
EXPERIMENTAL GERONTOLOGY, 2005, 40 (07) :612-614
[15]  
GAO JL, 1993, J BIOL CHEM, V268, P25395
[16]   Aspirin inhibits serine phosphorylation of insulin receptor substrate 1 in tumor necrosis factor-treated cells through targeting multiple serine kinases [J].
Gao, ZG ;
Zuberi, A ;
Quon, MJ ;
Dong, ZG ;
Ye, JP .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (27) :24944-24950
[17]   Inflammatory resolution: New opportunities for drug discovery [J].
Gilroy, DW ;
Lawrence, T ;
Perretti, M ;
Rossi, AG .
NATURE REVIEWS DRUG DISCOVERY, 2004, 3 (05) :401-416
[18]   Cutting edge: Lipoxins rapidly stimulate nonphlogistic phagocytosis of apoptotic neutrophils by monocyte-derived macrophages [J].
Godson, C ;
Mitchell, S ;
Harvey, K ;
Petasis, NA ;
Hogg, N ;
Brady, HR .
JOURNAL OF IMMUNOLOGY, 2000, 164 (04) :1663-1667
[19]   Lipoxin A4 and aspirin-triggered 15-epi-lipoxin A4 antagonize TNF-α-stimulated neutrophil-enterocyte interactions in vitro and attenuate TNF-α-induced chemokine release and colonocyte apoptosis in human intestinal mucosa ex vivo [J].
Goh, J ;
Baird, AW ;
O'Keane, C ;
Watson, RWG ;
Cottell, D ;
Bernasconi, G ;
Petasis, NA ;
Godson, C ;
Brady, HR ;
MacMathuna, P .
JOURNAL OF IMMUNOLOGY, 2001, 167 (05) :2772-2780
[20]   Insulin signaling diverges into Akt-dependent and -independent signals to regulate the recruitment/docking and the fusion of GLUT4 vesicles to the plasma membrane [J].
Gonzalez, Eva ;
McGraw, Timothy E. .
MOLECULAR BIOLOGY OF THE CELL, 2006, 17 (10) :4484-4493