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

Chavey, Carine; Lazennec, Gwendal; Lagarrigue, Sandrine; Clapé, Cyrielle; Iankova, Irena; Teyssier, Jacques; Annicotte, Jean-Sébastien; Schmidt, Julien; Mataki, Chikage; Yamamoto, Hiroyasu; Sanches, Rosario; Gumà, Anna; Štich, Vladimír; Vítková, Michaela; Jardin-Watelet, Bénédicte; Renard, Éric; Strieter, Robert M.; Tuthill, Antoinette; Hotamışlıgil, Gökhan S.; Vidal-Puig, António; Zorzano, António; Langin, Dominique; Fajas, Lluís

doi:10.1016/j.cmet.2009.03.002

Cited by 146 publications

(174 citation statements)

References 33 publications

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“…34 The alteration of MCP-1 levels mirrored the changes in the content of CD45 þ /14 þ cells, whereas CXCL5 already decreased after VLCD, as reported by Chavey et al 34 Nevertheless, we did not find correlation between these chemokines and ATM content. The lack of relation may be explained by the fact that these molecules are secreted into the circulation by various cells in different tissues.…”

Section: Discussioncontrasting

confidence: 49%

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

et al. 2010

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Objective: Accumulation of adipose tissue macrophages (ATMs) is observed in obesity and may participate in the development of insulin resistance and obesity-related complications. The aim of our study was to investigate the effect of long-term dietary intervention on ATM content in human adipose tissue. Design: We performed a multi-phase longitudinal study. Subjects and measurements: A total of 27 obese pre-menopausal women (age 39±2 years, body mass index 33.7±0.5 kg m -2 ) underwent a 6-month dietary intervention consisting of two periods: 4 weeks of very low-calorie diet (VLCD) followed by weight stabilization composed of 2 months of low-calorie diet and 3to 4 months of weight maintenance diet. At baseline and at the end of each dietary period, samples of subcutaneous adipose tissue (SAT) were obtained by needle biopsy and blood samples were drawn. ATMs were determined by flow cytometry using combinations of cell surface markers. Selected cytokine and chemokine plasma levels were measured using enzyme-linked immunosorbent assay. In addition, in a subgroup of 16 subjects, gene expression profiling of macrophage markers in SAT was performed using real-time PCR. Results: Dietary intervention led to a significant decrease in body weight, plasma insulin and C-reactive protein levels. After VLCD, ATM content defined by CD45 þ /14 þ /206 þ did not change, whereas it decreased at the end of the intervention. This decrease was associated with a downregulation of macrophage marker mRNA levels (CD14, CD163, CD68 and LYVE-1 (lymphatic vessel endothelial hyaluronan receptor-1)) and plasma levels of monocyte-chemoattractant protein-1 (MCP-1) and CXCL5 (chemokine (C-X-C motif) ligand 5). During the whole dietary intervention, the proportion of two ATM subpopulations distinguished by the CD16 marker was not changed. Conclusion: A 6-month weight-reducing dietary intervention, but not VLCD, promotes a decrease in the number of the whole ATM population with no change in the relative distribution of ATM subsets.

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Section: Discussioncontrasting

confidence: 49%

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

et al. 2010

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“…Previous studies have shown that MCP-1 triggers this macrophage infiltration and that modulation of the MCP-1/CCR2 signaling by genetic disruption or treatment with an inhibitory molecule can ameliorate obesity-induced insulin resistance (5,6,23,24,28). Other chemokines have recently been suggested to also promote macrophage infiltration in obesity (8,29,30). Receptors for these chemokines, including CCR2, are GPCRs, of which PI3Kγ lies downstream and mediates the signal to promote cell movement in response to chemokine stimulation (10,11,31,32).…”

Section: Discussionmentioning

confidence: 99%

“…Recent studies have revealed that obesity induces hematopoietic cell infiltration into adipose tissue, which in turn enhances adipose tissue inflammation and the secretion of proinflammatory adipokines, leading to systemic insulin resistance (3)(4)(5)(6)(7)(8). Inhibition of macrophage infiltration into adipose tissue could be considered a therapeutic strategy on the basis of the accumulated evidence of obesity-related metabolic disorders.…”

mentioning

confidence: 99%

Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

Kobayashi¹,

Ueki

Okazaki³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, lowgrade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg −/− ), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg −/− mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.

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“…However, very recent data strongly suggest that SOCS-2 is a key actor in modulating insulin signal in muscle. Indeed, it has been shown that chemokine CXC ligand-5 induces insulin resistance mainly by inhibiting insulin signalling in muscle, which may be driven by SOCS-2 production [36]. Moreover, a given SOCS protein appears to promote the proteasomal degradation of other SOCS proteins [37].…”

Section: Discussionmentioning

confidence: 99%

Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle leads to reduced mobility and overweight in mice

et al. 2009

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Aims/hypothesis Due to their ability to regulate various signalling pathways (cytokines, hormones, growth factors), the suppressor of cytokine signalling (SOCS) proteins are thought to be promising therapeutic targets for metabolic and inflammatory disorders. Hence, their role in vivo has to be precisely determined. Methods We generated transgenic mice constitutively producing SOCS-3 in skeletal muscle to define whether the sole abundance of SOCS-3 is sufficient to induce metabolic disorders and whether SOCS-3 is implicated in physiological roles distinct from metabolism. Results We demonstrate here that chronic expression of SOCS-3 in skeletal muscle leads to overweight in mice and worsening of high-fat diet-induced systemic insulin resistance. Counter-intuitively, insulin sensitivity in muscle of transgenic mice appears to be unaltered. However, following constitutive SOCS-3 production, several genes had deregu-P. Lebrun and E. Cognard contributed equally to this work. Electronic supplementary materialThe online version of this article

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

Cited by 146 publications

References 33 publications

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

Dietary intervention-induced weight loss decreases macrophage content in adipose tissue of obese women

Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

Constitutive expression of suppressor of cytokine signalling-3 in skeletal muscle leads to reduced mobility and overweight in mice

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