MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

Kanda, Hajime; Tateya, Sanshiro; Tamori, Yoshikazu; Kotani, Ko; Hiasa, Kenichi; Kitazawa, Riko; Kitazawa, Sohei; Miyachi, Hitoshi; Maeda, Sakan; Egashira, Kensuke; Kasuga, Masato

doi:10.1172/jci26498

Cited by 2,252 publications

(1,979 citation statements)

References 51 publications

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“…This hypothesis has been tested in transgenic mice that overexpress Mcp1 under the control of the adipose tissue-specific AP2 promoter. This study found that overexpression of Mcp1 in adipose tissue can enhance macrophage infiltration and cause insulin resistance [48,49]. Kanda et al went further to show that the onset of these abnormalities in obese mice could be prevented by genetic deletion of Mcp1 [48].…”

Section: Ccr2/mcp1mentioning

confidence: 90%

Inflammation and insulin resistance

2007

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Obesity-induced chronic inflammation is a key component in the pathogenesis of insulin resistance and the Metabolic syndrome. In this review, we focus on the interconnection between obesity, inflammation and insulin resistance. Proinflammatory cytokines can cause insulin resistance in adipose tissue, skeletal muscle and liver by inhibiting insulin signal transduction. The sources of cytokines in insulin resistant states are the insulin target tissue themselves, primarily fat and liver, but to a larger extent the activated tissue resident macrophages. While the initiating factors of this inflammatory response remain to be fully determined, chronic inflammation in these tissues could cause localized insulin resistance via autocrine/paracrine cytokine signaling and systemic insulin resistance via endocrine cytokine signaling all of which contribute to the abnormal metabolic state.

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Section: Ccr2/mcp1mentioning

confidence: 90%

Inflammation and insulin resistance

2007

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“…comparison, two recent studies in a high-fat diet model of obesity have suggested that transgenic overexpression of Ccl2 in adipose tissue promotes adipose macrophage accumulation and insulin resistance [27,28]. However, the aP2 promoter used in these experiments to drive transgenic Ccl2 expression is not specific for adipocytes and is also active in macrophages [29].…”

Section: Discussionmentioning

confidence: 99%

“…Since MCP-1 is known to activate macrophages [13,14], it is entirely feasible that the increased recruitment of macrophages into adipose tissue in these studies is facilitated by secretion of MCP-1 and other chemokines/cytokines by constitutively activated macrophages. One of these studies also found that a single intramuscular treatment with a plasmid encoding a human mutant form of Ccl2 (7ND), which dimerises with wild-type MCP-1 and inhibits its activity, was sufficient to reduce insulin resistance in obese db/db mice [27]. Surprisingly, the effect of 7ND treatment on blood glucose levels and macrophage accumulation in adipose tissue was not examined in these mice.…”

Section: Discussionmentioning

confidence: 99%

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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“…One of the inflammatory molecules that plays a role in the human ovulatory process and relates to both aging and obesity [14][15][16][17][18][19] is monocyte chemoattractant protein-1 (MCP-1) [20]. MCP-1, a polypeptide composed of 76 amino acids, is produced by various cell types including endothelial cells, fibroblasts, tumor cells, monocytes, and macrophages [20,21].…”

Section: Introductionmentioning

confidence: 99%

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

Merhi

Thornton

Bonney

et al. 2016

J Assist Reprod Genet

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Purpose The objective of this study was to test the hypothesis that ovarian kisspeptin (kiss1) and its receptor (kiss1r) expression are affected by age, obesity, and the age-and obesityrelated chemokine monocyte chemoattractant protein-1 (MCP-1). Methods Ovaries from reproductive-aged and older C57BL/ 6J mice fed normal chow (NC) or high-fat (HF) diet, ovaries from age-matched young MCP-1 knockout and young control mice on NC, and finally, cumulus and mural granulosa cells (GCs) from women who underwent in vitro fertilization (IVF) were collected. Kiss1, kiss1r, anti-Mullerian hormone (AMH), and AMH receptor (AMHR-II) messenger RNA (mRNA) expression levels were quantified using real-time polymerase chain reaction (RT-PCR).Results In mouse ovaries, kiss1 and kiss1r mRNA levels were significantly higher in old compared to reproductive-aged mice, and diet-induced obesity did not alter kiss1 or kiss1r mRNA levels. Compared to young control mice, young MCP-1 knockout mice had significantly lower ovarian kiss1 mRNA but significantly higher AMH and AMHR-II mRNA levels. In human cumulus GCs, kiss1r mRNA levels were positively correlated with age but not with BMI. There was no expression of kiss1 mRNA in either cumulus or mural GCs. Conclusion These data suggest a possible age-related physiologic role for the kisspeptinergic system in ovarian physiology. Additionally, the inflammatory MCP-1 may be associated with kiss1 and AMH genes, which are important in ovulation and folliculogenesis, respectively.

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MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity

Cited by 2,252 publications

References 51 publications

Inflammation and insulin resistance

Inflammation and insulin resistance

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

Ovarian kisspeptin expression is related to age and to monocyte chemoattractant protein-1

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