Monocyte chemoattractant protein-1 release is higher in visceral than subcutaneous human adipose tissue (AT): implication of macrophages resident in the AT.

UNLABELLED Human adipose tissue (AT) produces several adipokines including monocyte chemoattractant protein (MCP)-1, involved in the pathogenesis of atherosclerosis. OBJECTIVE Human AT cultures, isolated adipocytes, and stromal-vascular cells were used to investigate the relationship among AT-resident macrophages, MCP-1, and adiposity and the regulation of MCP-1. RESULTS mRNA levels of specific macrophage markers (CD68 and CD14) are correlated with adiposity in sc AT and visceral AT (P < 0.05). MCP-1 production is higher in stromal-vascular cells vs. adipocytes (P < 0.01) and correlates with macrophage markers in both AT compartments (P < 0.05). MCP-1 release is higher in obese subjects (P < 0.05) and in VAT (P < 0.01), but after adjusting for AT-resident macrophages, the differences disappear. MCP-1 is stimulated by IL-1beta, TNF-alpha, IL-8, IL-4, and IL-6 + IL-6-soluble receptor and is decreased by dexamethasone, IL-10, metformin, and thiazolidinediones. DISCUSSION MCP-1 is correlated with specific macrophage markers, adiposity, and AT localization, but the relationship seems to be related to the number of AT-resident macrophages. Despite this, MCP-1 may be involved in obesity-related health complications, and the decrease of MCP-1 by metformin and thiazolidinediones suggests that these antidiabetic compounds have antiinflammatory properties improving the low-grade inflammatory state observed in obesity.

[1]  B. Richelsen,et al.  Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects , 2005, International Journal of Obesity.

[2]  A. Aljada,et al.  Increased plasma concentration of macrophage migration inhibitory factor (MIF) and MIF mRNA in mononuclear cells in the obese and the suppressive action of metformin. , 2004, The Journal of clinical endocrinology and metabolism.

[3]  A. Aljada,et al.  Circulating Mononuclear Cells in the Obese Are in a Proinflammatory State , 2004, Circulation.

[4]  A. Aljada,et al.  Evidence for a potent antiinflammatory effect of rosiglitazone. , 2004, The Journal of clinical endocrinology and metabolism.

[5]  W. Boisvert.  Modulation of atherogenesis by chemokines. , 2004, Trends in cardiovascular medicine.

[6]  R. Busse,et al.  From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. , 2004, Diabetes.

[7]  R. Paschke,et al.  Monocyte chemoattractant protein 1 expression is stimulated by growth hormone and interleukin-6 in 3T3-L1 adipocytes. , 2004, Biochemical and biophysical research communications.

[8]  S. B. Pedersen,et al.  Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects , 2004, Molecular and Cellular Endocrinology.

[9]  A. Aljada,et al.  Inflammation: the link between insulin resistance, obesity and diabetes. , 2004, Trends in immunology.

[10]  A. Madan,et al.  Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue. , 2004, American journal of physiology. Endocrinology and metabolism.

[11]  M. Desai,et al.  Obesity is associated with macrophage accumulation in adipose tissue. , 2003, The Journal of clinical investigation.

[12]  L. Tartaglia,et al.  Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. , 2003, The Journal of clinical investigation.

[13]  H. Kotani,et al.  Adiposity Elevates Plasma MCP-1 Levels Leading to the Increased CD11b-positive Monocytes in Mice* , 2003, Journal of Biological Chemistry.

[14]  C. Heng,et al.  Childhood nephrotic syndrome in relapse is associated with down‐regulation of monocyte CD14 expression and lipopolysaccharide‐induced tumour necrosis factor‐α production , 2003, Clinical and experimental immunology.

[15]  S. Toubro,et al.  Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. , 2003, American journal of physiology. Endocrinology and metabolism.

[16]  Yoshiya Tanaka,et al.  Monocyte chemoattractant protein-1 induces scavenger receptor expression and monocyte differentiation into foam cells. , 2003, Biochemical and biophysical research communications.

[17]  H. Takaishi,et al.  High glucose accelerates MCP-1 production via p38 MAPK in vascular endothelial cells. , 2003, Biochemical and biophysical research communications.

[18]  D. Loskutoff,et al.  Monocyte chemoattractant protein 1 in obesity and insulin resistance , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[19]  E. Antman,et al.  Association Between Plasma Levels of Monocyte Chemoattractant Protein-1 and Long-Term Clinical Outcomes in Patients With Acute Coronary Syndromes , 2003, Circulation.

[20]  S. Bahouth,et al.  Resistin release by human adipose tissue explants in primary culture. , 2003, Biochemical and biophysical research communications.

[21]  S. Rose-John,et al.  The role of soluble receptors in cytokine biology: the agonistic properties of the sIL-6R/IL-6 complex. , 2002, Biochimica et biophysica acta.

[22]  I. Kowalska,et al.  Plasma interleukin-8 concentrations are increased in obese subjects and related to fat mass and tumor necrosis factor-alpha system. , 2002, The Journal of clinical endocrinology and metabolism.

[23]  Akira Takeshita,et al.  Anti-Monocyte Chemoattractant Protein-1 Gene Therapy Limits Progression and Destabilization of Established Atherosclerosis in Apolipoprotein E–Knockout Mice , 2002, Circulation.

[24]  A. Szuba,et al.  The role of chemokines in human cardiovascular pathology: enhanced biological insights. , 2002, Atherosclerosis.

[25]  W. Hsueh,et al.  PPARγ and Atherosclerosis , 2001 .

[26]  J. Takahara,et al.  Inhibition of monocyte chemoattractant protein-1 expression in cytokine-treated human lung epithelial cells by thiazolidinedione. , 2001, Chest.

[27]  L Wood,et al.  Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. , 2001, American journal of physiology. Endocrinology and metabolism.

[28]  A. Strosberg,et al.  Chemokines control fat accumulation and leptin secretion by cultured human adipocytes , 2001, Molecular and Cellular Endocrinology.

[29]  J. Després,et al.  Treatment of obesity: need to focus on high risk abdominally obese patients , 2001, BMJ : British Medical Journal.

[30]  A. Aljada,et al.  Suppression of nuclear factor-kappaB and stimulation of inhibitor kappaB by troglitazone: evidence for an anti-inflammatory effect and a potential antiatherosclerotic effect in the obese. , 2001, The Journal of clinical endocrinology and metabolism.

[31]  B. Richelsen,et al.  Regulation of interleukin 8 production and gene expression in human adipose tissue in vitro. , 2001, The Journal of clinical endocrinology and metabolism.

[32]  A. Baldwin.  Series Introduction: The transcription factor NF-κB and human disease , 2001 .

[33]  M. Nishikawa,et al.  Significance of chemokines and activated platelets in patients with diabetes , 2000, Clinical and experimental immunology.

[34]  E. Bruckert,et al.  Elevated levels of interleukin 6 are reduced in serum and subcutaneous adipose tissue of obese women after weight loss. , 2000, The Journal of clinical endocrinology and metabolism.

[35]  T Nakamura,et al.  Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. , 2000, Arteriosclerosis, thrombosis, and vascular biology.

[36]  S. B. Pedersen,et al.  Interleukin-8 Production in Human Adipose Tissue. Inhibitory Effects of Anti-Diabetic Compounds, the Thiazolidinedione Ciglitazone and the Biguanide Metformin , 2000, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[37]  F. Kato,et al.  Rapid fluorometric assay for cell viability and cell growth using nucleic acid staining and cell lysis agents. , 1999, Toxicology in vitro : an international journal published in association with BIBRA.

[38]  T. Ishida,et al.  Thiazolidinedione inhibits the production of monocyte chemoattractant protein‐1 in cytokine‐treated human vascular endothelial cells , 1999, FEBS letters.

[39]  R. Terkeltaub,et al.  Chemokines and atherosclerosis. , 1998, Current opinion in lipidology.

[40]  A. Greenberg,et al.  Journal of Clinical Endocrinology and Metabolism Printed in U.S.A. Copyright © 1998 by The Endocrine Society Omental and Subcutaneous Adipose Tissues of Obese Subjects Release Interleukin-6: Depot Difference and Regulation by Glucocorticoid* , 1997 .

[41]  S. Bulun,et al.  Expression of transcripts of interleukin-6 and related cytokines by human breast tumors, breast cancer cells, and adipose stromal cells , 1996, Molecular and Cellular Endocrinology.

[42]  B. Spiegelman,et al.  Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. , 1995, The Journal of clinical investigation.

[43]  B. Spiegelman,et al.  Tumor Necrosis Factor α: A Key Component of the Obesity-Diabetes Link , 1994, Diabetes.

[44]  R. Ross.  The pathogenesis of atherosclerosis--an update. , 1986, The New England journal of medicine.