Expression of CD68 and Macrophage Chemoattractant Protein-1 Genes in Human Adipose and Muscle Tissues

Gregorio, Gina B. Di; Yao-Borengasser, Aiwei; Rasouli, Neda; Varma, Vijayalakshmi; Lu, Tao; Miles, Leslie M.; Ranganathan, Gouri; Peterson, Charlotte A.; McGehee, Robert E.; Kern, Philip A.

doi:10.2337/diabetes.54.8.2305

Cited by 331 publications

(299 citation statements)

References 44 publications

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“…2A). In accordance with previous reports (3,5,6,26), stromalvascular cells abundantly express MCP1 and CD68 ( Fig. 2B and C), whereas the adipocyte fraction predominantly expresses adiponectin (Fig.…”

Section: G6pd and Inflammatory Signals In Adipocytessupporting

confidence: 78%

Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals

et al. 2006

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In adipocytes, oxidative stress and chronic inflammation are closely associated with metabolic disorders, including insulin resistance, obesity, cardiovascular disease, and type 2 diabetes. However, the molecular mechanisms underlying these metabolic disorders have not been thoroughly elucidated. In this report, we demonstrate that overexpression of glucose-6-phosphate dehydrogenase (G6PD) in adipocytes stimulates oxidative stress and inflammatory responses, thus affecting the neighboring macrophages. Adipogenic G6PD overexpression promotes the expression of pro-oxidative enzymes, including inducible nitric oxide synthase and NADPH oxidase, and the activation of nuclear factor-B (NF-B) signaling, which eventually leads to the dysregulation of adipocytokines and inflammatory signals. Furthermore, secretory factors from G6PD-overexpressing adipocytes stimulate macrophages to express more proinflammatory cytokines and to be recruited to the adipocytes; this would cause chronic inflammatory conditions in the adipose tissue of obesity. These effects of G6PD overexpression in adipocytes were abolished by pretreatment with NF-B inhibitors or antioxidant drugs. Thus, we propose that a high level of G6PD in adipocytes may mediate the onset of metabolic disorders in obesity by increasing the oxidative stress and inflammatory signals. Diabetes

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Section: G6pd and Inflammatory Signals In Adipocytessupporting

confidence: 78%

Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals

et al. 2006

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“…We performed a partial identification of other stromal cell types involved in AM synthesis. It is known that macrophages, frequently present in adipose tissue (25), produce AM in vitro (16,26). Our results demonstrate that AM and CD 68 proteins were colocalized, strongly suggesting that macrophages within adipose tissue can synthesize AM.…”

Section: Discussionsupporting

confidence: 61%

Expression of adrenomedullin in adipose tissue of lean and obese women

et al. 2006

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Objective: Adrenomedullin (AM), a potent vasodilatator and antioxidative peptide, was shown recently to be expressed by adipose tissue. The aim of our study was to investigate the precise localization of AM within human adipose tissue, and to examine AM regulation in obesity. Design: Subcutaneous (SC) and omental (OM) adipose tissues from 9 lean and 13 obese women were profiled for AM expression changes. Preadipocytes from human adipose tissue were isolated and differentiated under defined adipogenic conditions. Methods: AM expression was analyzed by immunohistochemistry, in situ hybridization and quantitative RT-PCR. Results: A strong AM expression was observed in vessel walls, stromal cell clusters and isolated stromal cells, some of them being CD 68 positive, whereas mature adipocytes were not labeled. Calcitonin receptor-like receptor and receptor activity-modifying proteins (RAMP) 2 and RAMP 3 were expressed in vessel walls. In vitro, preadipocytes of early differentiation stages spontaneously secreted AM. No difference in AM localization was found between SC and OM adipose tissue. AM levels in SC tissue did not differ between lean and obese subjects. By contrast, AM levels in OM tissue were significantly higher in obese as compared with lean women. Moreover, we found a positive relationship between OM AM and tumor necrosis factor a mRNA levels and AM-immunoreactive area in OM tissue followed the features of the metabolic syndrome. Conclusion: Stromal cells from human adipose tissue, including macrophages, produce AM. Its synthesis increased in the OM territory during obesity and paralleled the features of the metabolic syndrome. Therefore, AM should be considered as a new member of the adipokine family.

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“…These findings are also consistent with the development of glucose and insulin tolerance being similar in the two strains. In comparison, a human study recently showed that pioglitazone treatment improved insulin sensitivity in subjects with impaired glucose tolerance in association with reductions in MCP-1 and macrophages in subcutaneous adipose tissue, suggesting that these events were related [26]. However, on the basis of our present findings, it now appears likely that pioglitazone may have affected insulin sensitivity, MCP-1 levels and macrophage accrual through different mechanisms.…”

Section: Discussionsupporting

confidence: 58%

Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice

et al. 2006

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Aims/hypothesis Tissue macrophage accumulation is thought to induce insulin resistance during obesity and stimulate the progression of diabetic nephropathy. Monocyte chemoattractant protein-1 (MCP-1) is a potent stimulator of macrophage recruitment. It is increased in adipose tissue during obesity and in diabetic kidneys, suggesting that inflammation of these tissues may be MCP-1-dependent. Based on these findings, the aim of this study was to examine whether a deficiency in MCP-1 would alter the development of type 2 diabetes and its renal complications. Materials and methods The role of MCP-1 in the progression of type 2 diabetes and its associated renal injury was assessed in obese db/db mice that were deficient in the gene encoding MCP-1 (Ccl2). Results The incidence and development of type 2 diabetes were similar in Ccl2 +/+ and Ccl2 −/− db/db mice between 8 and 32 weeks of age. Body mass, hyperglycaemia, hyperinsulinaemia, glucose and insulin tolerance, plasma triacylglycerol and serum NEFA were not different between these strains. Pathological changes in epididymal adipose tissue, including increases in macrophage accumulation and Tnfa mRNA and reductions in Adipoq mRNA, were unaffected by the absence of MCP-1. In contrast, kidney macrophage accumulation and the progression of diabetic renal injury (albuminuria, histopathology, renal fibrosis) were substantially reduced in Ccl2 −/− compared with Ccl2 +/+ db/db mice with equivalent diabetes. Conclusions/interpretation Our study demonstrates that MCP-1 promotes type 2 diabetic renal injury but does not influence the development of obesity, insulin resistance or type 2 diabetes in db/db mice. MCP-1 plays a critical role in inflammation of the kidney, but not adipose tissue, during the progression of type 2 diabetes.

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Expression of CD68 and Macrophage Chemoattractant Protein-1 Genes in Human Adipose and Muscle Tissues

Cited by 331 publications

References 44 publications

Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals

Increase in Glucose-6-Phosphate Dehydrogenase in Adipocytes Stimulates Oxidative Stress and Inflammatory Signals

Expression of adrenomedullin in adipose tissue of lean and obese women

Monocyte chemoattractant protein-1-induced tissue inflammation is critical for the development of renal injury but not type 2 diabetes in obese db/db mice

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