Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin

Murdolo, Giuseppe; Hammarstedt, Ann; Sandqvist, Madeléne; Schmelz, Martin; Herder, Christian; Smith, Ulf; Jansson, Per‐Anders

doi:10.1210/jc.2006-2814

Cited by 49 publications

(42 citation statements)

References 42 publications

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“…We predicted that MIP-1␣ Ϫ/Ϫ mice would have lower fasting glucose and plasma insulin concentrations based on the improved insulin and glucose tolerance observed in other genetic models of chemokine deficiency, specifically in MCP-1 Ϫ/Ϫ , CCR2 Ϫ/Ϫ , and CXCL14 Ϫ/Ϫ mice (12, 20, 30) and the fact that expression of MIP-1␣ in WAT is positively correlated with fasting plasma insulin concentrations in humans (8,19,32). However, after 16 wk on WD, male MIP-1␣ Ϫ/Ϫ and MIP-1␣ ϩ/Ϫ mice had higher fasting blood glucose levels than male MIP-1␣ ϩ/ϩ mice, and blood glucose concentrations did not differ among female mice.…”

Section: Discussionmentioning

confidence: 99%

“…Expression of MIP-1␣ and its receptors CCR1 and CCR5 is increased in omental and subcutaneous WAT from obese humans compared with normalweight individuals (8). Furthermore, expression of MIP-1␣ and CCR1 in WAT is positively correlated with fasting plasma insulin concentrations in humans (8,19,32). Therefore, as multiple reports have shown, WAT MIP-1␣ transcript and protein are elevated in obesity and correlated with fasting plasma insulin; however, the consequences of this have not been established.…”

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confidence: 97%

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Absence of macrophage inflammatory protein-1α does not impact macrophage accumulation in adipose tissue of diet-induced obese mice

Surmi

Webb

Ristau

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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Surmi BK, Webb CD, Ristau AC, Hasty AH. Absence of macrophage inflammatory protein-1␣ does not impact macrophage accumulation in adipose tissue of diet-induced obese mice. Am J Physiol Endocrinol Metab 299: E437-E445, 2010. First published June 15, 2010; doi:10.1152/ajpendo.00050.2010.-Macrophages and T-lymphocytes are known to accumulate in the white adipose tissue (WAT) of obese mice and humans, but the factors that cause this infiltration are not yet determined. Chemokines, which attract leukocytes to inflammatory sites, are candidates for this process. Macrophage inflammatory protein-1␣ (MIP-1␣) expression is significantly elevated in WAT of obese mice and humans and positively correlates with fasting plasma insulin, but its potential role in leukocyte recruitment to WAT is unknown. MIP-1␣-deficient, heterozygous, and wild-type mice were fed a Western diet (WD) for 16 wk. Plasma lipids, adipose tissue mass, energy expenditure, food intake, liver triglyceride content, and inflammatory cytokine expression were not different among genotypes. Gene expression of macrophage markers F4/80 and CD68, as well as T-lymphocyte marker CD3ε was increased in perigonadal WAT of obese WD-fed mice but was not influenced by MIP-1␣ expression level. Immunohistochemical analysis of WAT also showed no effect of MIP-1␣ on macrophage content. Two related chemokines, MIP-1␤ and RANTES, had reduced expression in obese male MIP-1␣-deficient mice compared with wild-type controls (P Յ 0.05). In mice fed the WD for 6 wk, WAT macrophage content was unchanged; however, CD8ϩ T-lymphocytes accumulated to a lesser extent in the MIP-1␣-null mice. Therefore, expression of MIP-1␣, as well as that of MIP-1␤ and RANTES, increases as a consequence of weight gain, but these chemokines may not be required for the recruitment of monocytes to WAT during diet-induced obesity in mice and may impact T-lymphocyte recruitment only at early time points after WD feeding. chemokine; adipose tissue macrophage; macrophage inflammatory protein-1␤; regulated upon activation, normal T cell expressed and secreted PROINFLAMMATORY MACROPHAGES AND T-LYMPHOCYTES accumulate in the white adipose tissue (WAT) of obese mice and humans (6,14,22,25,31,(33)(34)(35). Research within this field has focused on multiple topics related to adipose tissue macrophages (ATMs) and T-lymphocytes, but many questions remain unanswered. In particular, although many different genes have been show to be upregulated in obese WAT, the individual contribution of many of these factors to the recruitment of immune cells to WAT has not been determined.One group of candidates for the recruitment of inflammatory cells into WAT is the family of "chemotactic cytokines," referred to as chemokines, which induce chemotaxis of leukocytes. According to their classic definition, chemokines are small, 8-to 10-kDa proteins that share structural similarity (1, 18). Chemokines have been implicated in chronic inflammatory diseases such as atherosclerosis and rheumatoid arthritis and, recently, obesity. Many chemo...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 97%

Absence of macrophage inflammatory protein-1α does not impact macrophage accumulation in adipose tissue of diet-induced obese mice

Surmi

Webb

Ristau

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

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“…Westerbacka et al have demonstrated that insulin-resistant humans have increased expression of macrophage markers in AT in comparison with insulin-sensitive individuals, and that AT expression of MCP-1 and MIP-1α is elevated during hyperinsulinemic euglycemic clamps in people with insulin resistance [63]. Furthermore, a significant positive correlation has been observed between gene expression of the chemokines MCP-1, MIP-1α and MCP-2 and fasting serum insulin as well as whole-body glucose disposal rate [62]. Finally, a recent study by Stulnig and colleagues demonstrated that expression of six different chemokines and their receptors was higher in obese compared with lean subjects, and the expression of CCL3 (MIP1-α) and CCL5 (RANTES) positively correlated with fasting plasma insulin levels independent of waist circumference [64].…”

Section: Chemokinesmentioning

confidence: 98%

“…Human studies-Multiple human studies have demonstrated an elevation in gene expression of various chemokines in AT in obesity, including MCP-1, MIP-1α, MIP-1β, MCP-2, MCP-4, MIP-2α and pulmonary and activation-regulated chemokine [15,62,63]. The expression of MCP-1 from the stromal vascular fraction of fat has been shown to be greater than its expression from the adipocyte fraction, and MCP-1 expression is positively correlated with the expression of macro-phage/monocyte markers CD68 and CD14 [9], providing evidence that macrophages are the main source of this chemokine in human AT.…”

Section: Chemokinesmentioning

confidence: 99%

Macrophage infiltration into adipose tissue: initiation, propagation and remodeling

2008

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It has long been known that adipose tissue in obesity is in a heightened state of inflammation. Recently, our understanding of this has been transformed by the knowledge that immune cells such as macrophages and T cells can infiltrate adipose tissue and are responsible for the majority of inflammatory cytokine production. These seminal findings have opened up a new area in biology that is garnering the interest of scientists involved in research relating to cell motility, inflammation, obesity, physiology, diabetes and cardiovascular disease. Some important general questions relevant to this field are: how are macrophages recruited to adipose tissue in obesity? What are the physiological consequences of macrophage-adipocyte interactions? Do these inflammatory macrophages contribute to pathophysiological conditions associated with obesity, such as insulin resistance, dyslipidemia, diabetes and cardiovascular disease? This review focuses on the first of these important questions. Keywords activation; adipose tissue; chemokines; crown-like structures; hypoxia; inflammation; insulin resistance; leptin; lymphocytes; macrophages During the past two decades, the complex nature of adipose tissue (AT) has become an area of intense investigation. This is in part due to the growing worldwide obesity epidemic, and in part to the identification of leptin as an adipokine secreted from AT. Since the discovery of leptin, many other adipokines, such as adiponectin, resistin, visfatin and omentin, have also been identified. These discoveries have led to the first revolution in the field of AT biology, the identification of AT as an endocrine organ. More recently, it has been discovered that not only adipocytes, but also immune cells, such as macrophages [1,2] and T lymphocytes [3][4][5], reside in AT, and that these cells may induce insulin resistance by promoting a proinflammatory milieu within the AT. This discovery has led to the second revolution in the field of AT biology,

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“…Hence, there might be differences in the inflammatory status of visceral adipose tissue in women with PCOS (36). However, it should be emphasized that the subcutaneous fat in the truncal region appears to contribute more to both the IR and the circulating NEFA pool than do adipose tissue depots elsewhere in the body (37), and it is not likely that the visceral tissue would directly account for the increased circulating concentrations of plasma cytokines and chemokines (38,39). Finally, CD11cC is not the only marker for staining M1-macrophages known in humans.…”

Section: Discussionmentioning

confidence: 99%

Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

Tao

Zhao

et al. 2012

European Journal of Endocrinology

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Objective: Alterations in the phenotypes of macrophages in adipose tissue play a key role in inflammation and insulin resistance (IR). The phenotypes of macrophages in subcutaneous adipose tissue (SAT) and the relationship between proinflammation markers and IR in women with polycystic ovary syndrome (PCOS) remain unclear. The objectives of this study are to characterize the gene expression of macrophage markers and cytokines in the SAT of PCOS women and to estimate their relationships with circulating levels of cytokines and IR. Methods: The cross-sectional study involves 16 PCOS women and 18 normal control women. Cytokines and macrophage markers in the circulation and SAT were determined using ELISA, quantitative PCR, or immunofluorescence staining. IR was estimated using the homeostasis model assessment (HOMA-IR). Results: The gene expression levels of CD11c along with TNFa and leptin in SAT remained significantly higher in PCOS women than in normal women (P!0.05). However, no significant differences were found in CD68 mRNA expression in SAT between women with and without PCOS (PO0.05). Furthermore, CD11c mRNA abundance provided a stronger contribution to models predicting serum levels of TNFa (sTNFa) than did CD68 mRNA abundance. Lastly, increased sTNFa was associated with increased HOMA-IR in PCOS women, and this association was independent of both overall and visceral adiposity. Conclusion: The high expression level of CD11c mRNA in SAT was proved to be an important feature in PCOS women. Furthermore, CD11c mRNA abundance made a stronger contribution to models predicting sTNFa in which existing proinflammatory properties might significantly contribute to the pathogenesis of IR in PCOS women.

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Monocyte Chemoattractant Protein-1 in Subcutaneous Abdominal Adipose Tissue: Characterization of Interstitial Concentration and Regulation of Gene Expression by Insulin

Cited by 49 publications

References 42 publications

Absence of macrophage inflammatory protein-1α does not impact macrophage accumulation in adipose tissue of diet-induced obese mice

Absence of macrophage inflammatory protein-1α does not impact macrophage accumulation in adipose tissue of diet-induced obese mice

Macrophage infiltration into adipose tissue: initiation, propagation and remodeling

Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

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