General Information:

Id: 1,203
Diseases: Diabetes mellitus, type II - [OMIM]
Insulin resistance
Obesity - [OMIM]
Mus musculus
male
article
Reference: Weisberg SP et al.(2006) CCR2 modulates inflammatory and metabolic effects of high-fat feeding J. Clin. Invest. 116: 115-124 [PMID: 16341265]

Interaction Information:

Comment In the adipose tissue of obese compared with lean mice, the expression of Ccl2 was increased 7.6-fold; Ccl7 was increased 8.4-fold; and Ccl8 was increased 2.1-fold.
Formal Description
Interaction-ID: 8029

disease

Obesity

increases_expression of

gene/protein

CCL2

Drugbank entries Show/Hide entries for CCL2
Comment In the adipose tissue of obese compared with lean mice, the expression of Ccl2 was increased 7.6-fold; Ccl7 was increased 8.4-fold; and Ccl8 was increased 2.1-fold.
Formal Description
Interaction-ID: 8030

disease

Obesity

increases_expression of

gene/protein

CCL7

Comment In the adipose tissue of obese compared with lean mice, the expression of Ccl2 was increased 7.6-fold; Ccl7 was increased 8.4-fold; and Ccl8 was increased 2.1-fold.
Formal Description
Interaction-ID: 8031

disease

Obesity

increases_expression of

gene/protein

CCL8

Drugbank entries Show/Hide entries for CCL8
Comment Treatment of obese mice with pioglitazone significantly decreased the expression of Ccr2, Ccl2, and Ccl7, but not Ccl8.
Formal Description
Interaction-ID: 8032

drug/chemical compound

Pioglitazone

decreases_expression of

gene/protein

CCR2

in obese mice
Drugbank entries Show/Hide entries for Pioglitazone
Comment Treatment of obese mice with pioglitazone significantly decreased the expression of Ccr2, Ccl2, and Ccl7, but not Ccl8.
Formal Description
Interaction-ID: 8033

drug/chemical compound

Pioglitazone

decreases_expression of

gene/protein

CCL2

in obese mice
Drugbank entries Show/Hide entries for Pioglitazone or CCL2
Comment Treatment of obese mice with pioglitazone significantly decreased the expression of Ccr2, Ccl2, and Ccl7, but not Ccl8.
Formal Description
Interaction-ID: 8034

drug/chemical compound

Pioglitazone

decreases_expression of

gene/protein

CCL7

in obese mice
Drugbank entries Show/Hide entries for Pioglitazone
Comment Treatment of obese mice with pioglitazone significantly decreased the expression of Ccr2, Ccl2, and Ccl7, but not Ccl8.
Formal Description
Interaction-ID: 8035

drug/chemical compound

Pioglitazone

NOT decreases_expression of

gene/protein

CCL8

in obese mice
Drugbank entries Show/Hide entries for Pioglitazone or CCL8
Comment Ccr2 deficiency attenuated but did not prevent the development of obesity in mice fed a high-fat diet.
Formal Description
Interaction-ID: 8036

gene/protein

CCR2

affects_activity of

phenotype

obesity, high-fat diet-induced

Comment Obese Ccr2-/- mice had lower fasting blood glucose and insulin concentrations compared with adiposity-matched obese Ccr2+/+ mice.
Formal Description
Interaction-ID: 8037

gene/protein

CCR2

affects_quantity of

drug/chemical compound

Glucose

in blood; in obese mice
Comment Adiposity-matched obese Ccr2-/- mice had 50% lower hepatic triglyceride content than obese Ccr2+/+ animals.
Formal Description
Interaction-ID: 8038

gene/protein

CCR2

affects_quantity of

drug/chemical compound

Triacylglycerol

in liver; in obese mice
Comment Despite having adipocytes that were larger and total adiposity that was equal, the adipose tissue macrophage (ATM) content of epididymal adipose tissue in obese Ccr2-/- mice was significantly less than the ATM content of adipose tissue in obese Ccr2+/+ mice.
Formal Description
Interaction-ID: 8039

gene/protein

CCR2

affects_quantity of

tissue/cell line

macrophage

in epididymal adipose tissue; in obese mice
Comment Obese Ccr2+/+ mice compared with lean Ccr2+/+ mice showed increased expression of genes encoding proinflammatory molecules including Tnfa (TNF-alpha) and Serpine1 (plasminogen activator inhibitor-1 [PAI-1]) and the macrophage markers Emr1 (F4/80) and Cd68 (CD68).
Formal Description
Interaction-ID: 8040

disease

Obesity

increases_expression of

gene/protein

TNF

Drugbank entries Show/Hide entries for TNF
Comment Obese Ccr2+/+ mice compared with lean Ccr2+/+ mice showed increased expression of genes encoding proinflammatory molecules including Tnfa (TNF-alpha) and Serpine1 (plasminogen activator inhibitor-1 [PAI-1]) and the macrophage markers Emr1 (F4/80) and Cd68 (CD68).
Formal Description
Interaction-ID: 8041

disease

Obesity

increases_expression of

gene/protein

SERBP1

Comment Obese Ccr2+/+ mice compared with lean Ccr2+/+ mice showed increased expression of genes encoding proinflammatory molecules including Tnfa (TNF-alpha) and Serpine1 (plasminogen activator inhibitor-1 [PAI-1]) and the macrophage markers Emr1 (F4/80) and Cd68 (CD68).
Formal Description
Interaction-ID: 8042

disease

Obesity

increases_expression of

gene/protein

EMR1

Comment Obese Ccr2+/+ mice compared with lean Ccr2+/+ mice showed increased expression of genes encoding proinflammatory molecules including Tnfa (TNF-alpha) and Serpine1 (plasminogen activator inhibitor-1 [PAI-1]) and the macrophage markers Emr1 (F4/80) and Cd68 (CD68).
Formal Description
Interaction-ID: 8043

disease

Obesity

increases_expression of

gene/protein

CD68

Comment Expression of the macrophage markers Emr1 and Cd68 was reduced in obese Ccr2-/- mice compared with obese Ccr2+/+ mice.
Formal Description
Interaction-ID: 8044

gene/protein

CCR2

affects_expression of

gene/protein

EMR1

in obese mice
Comment Expression of the macrophage markers Emr1 and Cd68 was reduced in obese Ccr2-/- mice compared with obese Ccr2+/+ mice.
Formal Description
Interaction-ID: 8045

gene/protein

CCR2

affects_expression of

gene/protein

CD68

in obese mice
Comment Tnfa expression was reduced in obese Ccr2-/- mice.
Formal Description
Interaction-ID: 8046

gene/protein

CCR2

affects_expression of

gene/protein

TNF

in obese mice
Drugbank entries Show/Hide entries for TNF
Comment No significant differences in the expression of Emr1, Cd68 and Tnfa were observed between lean Ccr2-/- and Ccr2+/+ mice, nor were differences observed in Serpine1, Ccl2, or Ccl7 expression between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8047

gene/protein

CCR2

NOT affects_expression of

gene/protein

EMR1

in lean mice
Comment No significant differences in the expression of Emr1, Cd68 and Tnfa were observed between lean Ccr2-/- and Ccr2+/+ mice, nor were differences observed in Serpine1, Ccl2, or Ccl7 expression between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8048

gene/protein

CCR2

NOT affects_expression of

gene/protein

CD68

in lean mice
Comment No significant differences in the expression of Emr1, Cd68 and Tnfa were observed between lean Ccr2-/- and Ccr2+/+ mice, nor were differences observed in Serpine1, Ccl2, or Ccl7 expression between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8049

gene/protein

CCR2

NOT affects_expression of

gene/protein

TNF

in lean mice
Drugbank entries Show/Hide entries for TNF
Comment No significant differences in the expression of Emr1, Cd68 and Tnfa were observed between lean Ccr2-/- and Ccr2+/+ mice, nor were differences observed in Serpine1, Ccl2, or Ccl7 expression between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8050

gene/protein

CCR2

NOT affects_expression of

gene/protein

SERBP1

in obese mice
Comment No significant differences in the expression of Emr1, Cd68 and Tnfa were observed between lean Ccr2-/- and Ccr2+/+ mice, nor were differences observed in Serpine1, Ccl2, or Ccl7 expression between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8051

gene/protein

CCR2

NOT affects_expression of

gene/protein

CCL2

in obese mice
Drugbank entries Show/Hide entries for CCL2
Comment No significant differences in the expression of Emr1, Cd68 and Tnfa were observed between lean Ccr2-/- and Ccr2+/+ mice, nor were differences observed in Serpine1, Ccl2, or Ccl7 expression between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8052

gene/protein

CCR2

NOT affects_expression of

gene/protein

CCL7

in obese mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8053

gene/protein

CCR2

affects_expression of

gene/protein

GPAM

in obese mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8054

gene/protein

CCR2

NOT affects_expression of

gene/protein

GPAM

in lean mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8055

gene/protein

CCR2

affects_expression of

gene/protein

LIPE

in obese mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8056

gene/protein

CCR2

NOT affects_expression of

gene/protein

LIPE

in lean mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8057

gene/protein

CCR2

affects_expression of

gene/protein

FABP4

in obese mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8058

gene/protein

CCR2

NOT affects_expression of

gene/protein

FABP4

in lean mice
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8059

gene/protein

CCR2

affects_expression of

gene/protein

PPARG

in obese mice
Drugbank entries Show/Hide entries for PPARG
Comment The expression of 4 genes downregulated in obesity and by Ccl2 treatment of adipocytes was measured: a nuclear encoded mitochondrial gene (Gpam), a lipase (Lipe), a fatty acid binding protein (Fabp4), and a transcription factor required for adipocyte differentiation (Pparg). In lean animals there was no effect of Ccr2 genotype on the expression of these genes, but in obese mice the expression of these genes was increased in Ccr2-/- compared with Ccr2+/+ mice.
Formal Description
Interaction-ID: 8060

gene/protein

CCR2

NOT affects_expression of

gene/protein

PPARG

in lean mice
Drugbank entries Show/Hide entries for PPARG
Comment In epididymal adipose tissue of obese Ccr2-/- mice genes involved in the regulation of immune responses (GO:0050778), interleukin receptor activity (GO:0004907), and NF-kappaB signaling (GO:0043122) were downregulated.
Formal Description
Interaction-ID: 8061

gene/protein

CCR2

affects_activity of

in epididymal adipose tissue; in obese mice
Comment In epididymal adipose tissue of obese Ccr2-/- mice genes involved in the regulation of immune responses (GO:0050778), interleukin receptor activity (GO:0004907), and NF-kappaB signaling (GO:0043122) were downregulated.
Formal Description
Interaction-ID: 8062

gene/protein

CCR2

affects_activity of

complex/PPI

Cytokine receptor

in epididymal adipose tissue; in obese mice
Comment In epididymal adipose tissue of obese Ccr2-/- mice genes involved in the regulation of immune responses (GO:0050778), interleukin receptor activity (GO:0004907), and NF-kappaB signaling (GO:0043122) were downregulated.
Formal Description
Interaction-ID: 8063

gene/protein

CCR2

affects_activity of

in epididymal adipose tissue; in obese mice
Comment Several individual genes with higher levels of expression in Ccr2-/- than in Ccr2+/+ obese mice encode hormones produced by adipocytes, including leptin (Lep), resistin (Retn), and adiponectin (Acdc).
Formal Description
Interaction-ID: 8064

gene/protein

CCR2

affects_expression of

gene/protein

LEP

in adipose tissue; in obese mice
Comment Several individual genes with higher levels of expression in Ccr2-/- than in Ccr2+/+ obese mice encode hormones produced by adipocytes, including leptin (Lep), resistin (Retn), and adiponectin (Acdc).
Formal Description
Interaction-ID: 8065

gene/protein

CCR2

affects_expression of

gene/protein

RETN

in adipose tissue; in obese mice
Comment Several individual genes with higher levels of expression in Ccr2-/- than in Ccr2+/+ obese mice encode hormones produced by adipocytes, including leptin (Lep), resistin (Retn), and adiponectin (Acdc).
Formal Description
Interaction-ID: 8066

gene/protein

CCR2

affects_expression of

gene/protein

ADIPOQ

in adipose tissue; in obese mice
Comment Despite alterations in adipose tissue gene expression, no differences in circulating concentrations of leptin or resistin were detected between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8067

gene/protein

CCR2

NOT affects_quantity of

gene/protein

LEP

in blood; in obese mice
Comment Despite alterations in adipose tissue gene expression, no differences in circulating concentrations of leptin or resistin were detected between obese Ccr2-/- and Ccr2+/+ mice.
Formal Description
Interaction-ID: 8068

gene/protein

CCR2

NOT affects_quantity of

gene/protein

RETN

in blood; in obese mice
Comment The amount of circulating adiponectin in plasma, while similar in lean mice of both genotypes, was significantly higher in obese mice deficient in Ccr2 than in wild-type obese animals.
Formal Description
Interaction-ID: 8069

gene/protein

CCR2

affects_quantity of

gene/protein

ADIPOQ

in blood; in obese mice
Comment The amount of circulating adiponectin in plasma, while similar in lean mice of both genotypes, was significantly higher in obese mice deficient in Ccr2 than in wild-type obese animals.
Formal Description
Interaction-ID: 8070

gene/protein

CCR2

NOT affects_quantity of

gene/protein

ADIPOQ

in blood; in lean mice
Comment IL-6 and PAI-1 are circulating proteins that are produced by multiple organs and tissues including adipose tissue, liver, leukocytes, and endothelial cells. Both have been implicated in obesity-induced insulin resistance, and the adipose tissue expression of both is increased in obesity. No Ccr2-dependent modulation in adipose tissue expression of IL-6 or PAI-1 was detected.
Formal Description
Interaction-ID: 8071

gene/protein

CCR2

NOT affects_expression of

gene/protein

IL6

in adipose tissue
Drugbank entries Show/Hide entries for IL6
Comment IL-6 and PAI-1 are circulating proteins that are produced by multiple organs and tissues including adipose tissue, liver, leukocytes, and endothelial cells. Both have been implicated in obesity-induced insulin resistance, and the adipose tissue expression of both is increased in obesity. No Ccr2-dependent modulation in adipose tissue expression of IL-6 or PAI-1 was detected.
Formal Description
Interaction-ID: 8072

gene/protein

CCR2

NOT affects_expression of

gene/protein

SERPINE1

in adipose tissue
Drugbank entries Show/Hide entries for SERPINE1
Comment Consistent with the gene expression data, there were no CCR2-dependent alterations in the circulating concentration of IL-6. In contrast, lower circulating concentrations of PAI-1 in lean and obese Ccr2-/- mice were detected when compared with weightmatched Ccr2+/+ mice. These data reveal that CCR2 modulates circulating PAI-1 by a mechanism that is not primarily dependent upon adipose tissue expression or the development of obesity.
Formal Description
Interaction-ID: 8073

gene/protein

CCR2

NOT affects_quantity of

gene/protein

IL6

in blood
Drugbank entries Show/Hide entries for IL6
Comment Consistent with the gene expression data, there were no CCR2-dependent alterations in the circulating concentration of IL-6. In contrast, lower circulating concentrations of PAI-1 in lean and obese Ccr2-/- mice were detected when compared with weightmatched Ccr2+/+ mice. These data reveal that CCR2 modulates circulating PAI-1 by a mechanism that is not primarily dependent upon adipose tissue expression or the development of obesity.
Formal Description
Interaction-ID: 8074

gene/protein

CCR2

affects_quantity of

gene/protein

SERPINE1

in blood
Drugbank entries Show/Hide entries for SERPINE1
Comment Obese Ccr2-/- mice had lower fasting blood glucose and insulin concentrations compared with adiposity-matched obese Ccr2+/+ mice.
Formal Description
Interaction-ID: 13360

gene/protein

CCR2

affects_quantity of

complex/PPI

Insulin

in blood; in obese mice