CXC Ligand 5 Is an Adipose-Tissue Derived Factor that Links Obesity to Insulin Resistance

被引：148

作者：

Chavey, Carine ^{[1
,2
]}

Lazennec, Gwendal ^{[3
]}

Lagarrigue, Sylviane ^{[1
,2
]}

Clape, Cyrielle ^{[1
,2
]}

Iankova, Irena ^{[1
,2
]}

Teyssier, Jacques ^{[1
,2
]}

Annicotte, Jean-Sebastien ^{[1
,2
]}

Schmidt, Julien ^{[1
,2
]}

Mataki, Chikage ^{[15
]}

Yamamoto, Hiroyasu ^{[15
]}

Sanches, Rosario ^{[4
,5
]}

Guma, Anna ^{[4
,5
]}

Stich, Vladimir ^{[6
,7
]}

Vitkova, Michaela ^{[6
,7
]}

Jardin-Watelet, Benedicte ^{[8
]}

Renard, Eric ^{[9
]}

Strieter, Robert ^{[10
]}

Tuthill, Antoinette ^{[11
]}

Hotamisligil, Gokhan S. ^{[16
]}

Vidal-Puig, Antonio ^{[11
]}

Zorzano, Antonio

Langin, Dominique ^{[6
,7
,12
,13
,14
]}

Fajas, Lluis ^{[1
,2
,9
]}

机构：

[1] Univ Montpellier I, INSERM U834, U896, CRLC Val Aurelle,U834, F-34295 Montpellier, France

[2] Inst Rech Cancerol Montpellier, IRCM, F-34298 Montpellier, France

[3] INSERM, U844, F-34295 Montpellier, France

[4] Univ Barcelona, Inst Biomed Res, E-08028 Barcelona, Spain

[5] Univ Barcelona, Dept Bioquim Biol Mol, Fac Biol, E-08028 Barcelona, Spain

[6] Charles Univ Prague, Francoczech Lab Clin Res Obes, INSERM, CZ-10000 Prague, Czech Republic

[7] Charles Univ Prague, Fac Med 3, CZ-10000 Prague, Czech Republic

[8] Cap Delta, CNRS, Biorad FRE3009, F-34184 Montpellier, France

[9] Ctr Hosp Univ Montpellier, F-34295 Montpellier, France

[10] Univ Virginia, Dept Med, Charlottesville, VA 22908 USA

[11] Univ Cambridge, Metab Res Labs, Inst Metab Sci, Addenbrookes Hosp, Cambridge CB2 2QR, England

[12] INSERM, U858, Obes Res Lab, F-31432 Toulouse, France

[13] Univ Toulouse 3, Louis Bugnard Inst, IFR31, F-31432 Toulouse, France

[14] CHU Toulouse, Biochem Lab, Biol Inst Purpan, F-31059 Toulouse, France

[15] CNRS, INSERM, ULP, Inst Genet & Biol Mol & Cellulaire, F-67404 Illkirch Graffenstaden, France

[16] Harvard Univ, Sch Publ Hlth, Dept Genet & Complex Dis, Boston, MA 02115 USA

来源：

CELL METABOLISM | 2009年 / 9卷 / 04期

基金：

英国医学研究理事会; 美国国家卫生研究院;

关键词：

ACTIVATED-RECEPTOR-GAMMA; PEPTIDE ENA-78; CHEMOATTRACTANT PROTEIN-1; PROMOTES ADIPOGENESIS; ENERGY-BALANCE; INFLAMMATION; EXPRESSION; ACCUMULATION; MACROPHAGES; ADIPOCYTES;

D O I：

10.1016/j.cmet.2009.03.002

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

We show here high levels of expression and secretion of the chemokine CXC ligand 5 (CXCL5) in the macrophage fraction of white adipose tissue (WAT). Moreover, we find that CXCL5 is dramatically increased in serum of human obese compared to lean subjects. Conversely, CXCL5 concentration is decreased in obese subjects after a weight reduction program, or in obese non-insulin-resistant, compared to insulin-resistant, subjects. Most importantly we demonstrate that treatment with recombinant CXCL5 blocks insulin-stimulated glucose uptake in muscle in mice. CXCL5 blocks insulin signaling by activating the Jak2/STAT5/SOCS2 pathway. Finally, by treating obese, insulin-resistant mice with either anti-CXCL5 neutralizing antibodies or antagonists of CXCR2, which is the CXCL5 receptor, we demonstrate that CXCL5 mediates insulin resistance. Furthermore CXCR2-/- mice are protected against obesity-induced insulin resistance. Taken together, these results show that secretion of CXCL5 by WAT resident macrophages represents a link between obesity, inflammation, and insulin resistance.

引用

页码：339 / 349

页数：11

共 32 条

[1] Cdk4 promotes adipogenesis through PPARγ activation [J].

Abella, A ;

Dubus, P ;

Malumbres, M ;

Rane, SG ;

Kiyokawa, H ;

Sicard, A ;

Vignon, F ;

Langin, D ;

Barbacid, M ;

Fajas, L .

CELL METABOLISM, 2005, 2 (04) :239-249

[2] Adipose tissue as an endocrine organ [J].

Ahima, RS ;

Flier, JS .

TRENDS IN ENDOCRINOLOGY AND METABOLISM, 2000, 11 (08) :327-332

[3] Peroxisome proliferator-activated receptor γ regulates E-cadherin expression and inhibits growth and invasion of prostate cancer [J].

Annicotte, Jean-Sebastien ;

Iankova, Irena ;

Miard, Stephanie ;

Fritz, Vanessa ;

Sarruf, David ;

Abella, Anna ;

Berthe, Marie-Laurence ;

Noel, Daniele ;

Pillon, Arnaud ;

Iborra, Francois ;

Dubus, Pierre ;

Maudelonde, Thierry ;

Culine, Stephane ;

Fajas, Lluis .

MOLECULAR AND CELLULAR BIOLOGY, 2006, 26 (20) :7561-7574

[4] The nuclear receptor liver receptor homolog-1 is an estrogen receptor target gene [J].

Annicotte, JS ;

Chavey, C ;

Servant, N ;

Teyssier, J ;

Bardin, A ;

Licznar, A ;

Badia, E ;

Pujol, P ;

Vignon, F ;

Maudelonde, T ;

Lazennec, G ;

Cavailles, V ;

Fajas, L .

ONCOGENE, 2005, 24 (55) :8167-8175

[5] Epithelial-neutrophil activating peptide (ENA-78) is an important angiogenic factor in non-small cell lung cancer [J].

Arenberg, DA ;

Keane, MP ;

DiGiovine, B ;

Kunkel, SL ;

Morris, SB ;

Xue, YY ;

Burdick, MD ;

Glass, MC ;

Iannettoni, MD ;

Strieter, RM .

JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (03) :465-472

[6] The adipocyte as an active participant in energy balance and metabolism [J].

Badman, Michael K. ;

Flier, Jeffrey S. .

GASTROENTEROLOGY, 2007, 132 (06) :2103-2115

[7] Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects [J].

Clément, K ;

Viguerie, N ;

Poitou, C ;

Carette, C ;

Pelloux, V ;

Curat, CA ;

Sicard, A ;

Rome, S ;

Benis, A ;

Zucker, JD ;

Vidal, H ;

Laville, M ;

Barsh, GS ;

Basdevant, A ;

Stich, V ;

Cancello, R ;

Langin, D .

FASEB JOURNAL, 2004, 18 (14) :1657-1669

[8] Macrophages in human visceral adipose tissue:: increased accumulation in obesity and a source of resistin and visfatin [J].

Curat, CA ;

Wegner, V ;

Sengenès, C ;

Miranville, A ;

Tonus, C ;

Busse, R ;

Bouloumié, A .

DIABETOLOGIA, 2006, 49 (04) :744-747

[9] Expression of CD68 and macrophage chemoattractant protein-1 genes in human adipose and muscle tissues - Association with cytokine expression, insulin resistance, and reduction by pioglitazone [J].

Di Gregorio, GB ;

Yao-Borengasser, A ;

Rasouli, N ;

Varma, V ;

Lu, T ;

Miles, LM ;

Ranganathan, G ;

Peterson, CA ;

McGehee, RE ;

Kern, PA .

DIABETES, 2005, 54 (08) :2305-2313

[10]

Halloran MM, 1999, J IMMUNOL, V162, P7492

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