Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P80098 (monocyte chemoattractant protein)
 1,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arterial stiffness is an independent risk factor for cardiovascular events in diabetic patients, and it can be assessed by measuring pulse wave velocity (PWV). We investigated the degree of arterial stiffness in diabetic patients with coronary artery disease (CAD) and the effect of the proliferator-activated receptor gamma (PPAR-gamma) agonist rosiglitazone on arterial stiffness in the potential mechanism of anti-arteriosclerosis in patients with type 2 diabetes mellitus and CAD. The 123 participants were divided into 3 groups: healthy controls (n = 36), diabetic patients (n = 41), and diabetic patients with CAD (n = 46). Forty-six diabetic patients with CAD were randomly divided into 2 groups: untreated diabetic patients with CAD and diabetic patients with CAD treated with 4 mg/d of rosiglitazone (n = 25) for 12 weeks. Pulse wave velocity was measured before treatment and at 12-week follow-up. Baseline PWV was significantly higher in patients with diabetes, diabetes and CAD, and diabetes and CAD with treatment as compared with the healthy control group (1,633 +/- 37.3, 1,669 +/- 53.8, 1,615 +/- 44.4, and 1,360 +/- 39.9 cm/s, respectively, P < .001). Pulse wave velocity in the rosiglitazone-treated group was significantly reduced, from 1,615 +/- 44.4 to 1,525 +/- 43.1 cm/s, after 12-week treatment, Furthermore, PWV was significantly decreased in the rosiglitazone-treated group compared with untreated group after 12 weeks (1525 +/- 43.1 and 1,670 +/- 41.3 cm/s, respectively). Pulse wave velocity in the untreated group did not differ from baseline levels after 12 weeks. In addition, plasma C-reactive protein level was decreased significantly in the rosiglitazone-treated group compared with values at baseline and for the untreated group after 12 weeks (0.73 +/- 0.09, 1.71 +/- 0.24, and 1.33 +/- 0.29 mg/L, respectively). Plasma level of monocyte chemoattractant protein 1 was decreased in the rosiglitazone group compared with the level at baseline (392 +/- 42 and 273 +/- 40 pg/mL, respectively). Moreover, the decrease in PWV was associated linearly both with improved homeostasis model assessment of insulin resistance and with decreased C-reactive protein level after PPAR-gamma agonist treatment. In conclusion, PPAR-gamma agonist rosiglitazone treatment may significantly decrease arterial stiffness in diabetic patients with CAD. Proliferator-activated receptor gamma agonists may play an important role in protecting against arteriosclerosis by normalizing the metabolic disorders and depressing chronic inflammation of the vascular system in patients with type 2 diabetes mellitus and serious vascular disease.
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PMID:Peroxisome proliferator-activated receptor gamma agonist improves arterial stiffness in patients with type 2 diabetes mellitus and coronary artery disease. 1788 51

Obese adipose tissue is characterized by an enhanced infiltration of macrophages. It is considered that the paracrine loop involving monocyte chemoattractant protein (MCP)-1 and tumor necrosis factor (TNF)-alpha between adipocytes and macrophages establishes a vicious cycle that augments the inflammatory changes and insulin resistance in obese adipose tissue. Polyphenols, which are widely distributed in fruit and vegetables, can act as antioxidants and some of them are also reported to have anti-inflammatory properties. Tomato is one of the most popular and extensively consumed vegetable crops worldwide, which also contains many flavonoids, mainly naringenin chalcone. We investigated the effect of flavonoids, including naringenin chalcone, on the production of proinflammatory mediators in lipopolysaccharide (LPS)-stimulated macrophages and in the interaction between adipocytes and macrophages. Naringenin chalcone inhibited the production of TNF-alpha, MCP-1, and nitric oxide (NO) by LPS-stimulated RAW 264 macrophages in a dose-dependent manner. Coculture of 3T3-L1 adipocytes and RAW 264 macrophages markedly enhanced the production of TNF-alpha, MCP-1, and NO compared with the control cultures; however, treatment with naringenin chalcone dose-dependently inhibited the production of these proinflammatory mediators. These results indicate that naringenin chalcone exhibits anti-inflammatory properties by inhibiting the production of proinflammatory cytokines in the interaction between adipocytes and macrophages. Naringenin chalcone may be useful for ameliorating the inflammatory changes in obese adipose tissue.
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PMID:Inhibitory effect of naringenin chalcone on inflammatory changes in the interaction between adipocytes and macrophages. 1791 59

Adipokines play crucial roles in obesity-related insulin resistance in adults, but little is known in the general adolescent population. This study was designed to investigate the relationships between adipokines and metabolic parameters, the insulin resistance index, and proinflammatory cytokines in the general population of Japanese male adolescents. We studied 662 Japanese male high school students aged 16 to 17 years and 282 healthy Japanese male adults aged 30 to 61 years who received annual health checkups. High-molecular weight (HMW) adiponectin levels were significantly lower in adolescents (4.18 +/- 2.24 microg/mL) than in adults (4.84 +/- 3.20 microg/mL), despite body mass index (BMI) being significantly lower in adolescents. The HMW adiponectin levels correlated negatively with BMI and the homeostasis model assessment of insulin resistance index (HOMA-IR) in adults. In adolescents, HMW adiponectin correlated negatively with BMI and waist circumference, but not with HOMA-IR or other metabolic parameters except high-density lipoprotein cholesterol. Leptin levels correlated positively with HOMA-IR, triglycerides, tumor necrosis factor alpha, interleukin 6, and monocyte chemoattractant protein 1 and negatively with high-density lipoprotein cholesterol even after adjustment for BMI. These findings suggest that serum leptin is a more useful biomarker of fat accumulation-related insulin resistance, inflammation, and metabolic abnormalities than HMW adiponectin in the general population of male adolescents. The inverse correlation between adiponectin and insulin resistance may manifest in the later phase of obesity development.
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PMID:Significance of leptin and high-molecular weight adiponectin in the general population of Japanese male adolescents. 1819 Oct 43

CCL2 (MCP-1, monocyte chemoattractant protein 1) and CCL3 (MIP-1alpha, macrophage inflammatory protein 1alpha) are required for macrophage infiltration in adipose tissue. Insulin increases CCL2 expression in adipose tissue and in serum more in insulin-resistant obese than in insulin-sensitive lean mice, but whether this is true in humans is unknown. We compared basal expression and insulin regulation of CCL2 and CCL3 in adipose tissue and MCP-1 and MIP-1alpha in serum between insulin-resistant and insulin-sensitive human subjects. Subcutaneous adipose tissue biopsies and blood samples were obtained before and at the end of 6 h of in vivo euglycemic hyperinsulinemia (maintained by the insulin clamp technique) in 11 lean insulin-sensitive and 10 obese insulin-resistant women, and before and after a 6-h saline infusion in 8 women. Adipose tissue mRNA concentrations of monocyte/macrophage markers CD68, EMR1, ITGAM, ADAM8, chemokines CCL2 and CCL3, and housekeeping gene ribosomal protein large P0 (RPLP0) were measured by means of real-time PCR at baseline. In addition, mRNA concentrations of CCL2, CCL3, and RPLP0 were measured after insulin infusion. Levels of MCP-1 and MIP-1alpha were determined in serum, and protein concentration of MCP-1 was determined in adipose tissue at baseline and after insulin infusion. Basally, expression of the macrophage markers CD68 and EMR1 were increased in adipose tissue of insulin-resistant subjects. Insulin increased MCP-1 gene and protein expression significantly more in the insulin-resistant than in the insulin-sensitive subjects. Basally expression of CCL2 and CCL3 and expression of macrophage markers CD68 and ITGAM were significantly correlated. In serum, MCP-1 decreased significantly in insulin-sensitive but not insulin-resistant subjects. MIP-1alpha was undetectable in serum. Insulin regulation of CCL2 differs between insulin-sensitive and -resistant subjects in a direction that could exacerbate adipose tissue inflammation.
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PMID:Insulin regulation of MCP-1 in human adipose tissue of obese and lean women. 1827 Mar

In Western culture, excess visceral fat accumulation or obesity has reached epidemic proportions, resulting in metabolic syndrome. However, more than 10 years of research has shown that adipocytes also function as endocrine cells that release various bioactive substances, so called "adipocytokines or adipokines", that play a major role in the regulation of food intake, insulin sensitivity, energy metabolism, and the vascular microenvironment. Adiponectin, an adipocytokine, is considered to improve insulin sensitivity. Recently, monocyte chemoattractant protein (MCP)-1 has been reported to be a novel adipocytokine involved in the development of obesity-associated insulin resistance and atherosclerosis. Nuclear receptors, especially peroxisome proliferator-activated receptor-alpha (PPAR alpha) and PPAR gamma are ligand-activated transcription factors that regulate the metabolism of glucose and lipids. PPAR gamma is strongly expressed in adipocytes and plays a significant role in the transcriptional activation of adipocytokines including adiponectin. PPAR alpha, another PPAR isoform, is involved in the control of lipid metabolism in the liver and skeletal muscle. PPAR alpha activation causes lipid clearance via beta-oxidation enhancement. We showed that various dietary terpenoids and other natural ingredients regulate the transcription of PPAR target genes, induces the expression and secretion of adiponectin, and inhibits those of MCP-1 in adipocytes and beta-oxidation in liver. These findings indicate that dietary factor acts as an agonist of PPARs and is a valuable medical and food component for the gradual improvement of metabolic syndrome.
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PMID:Dietary regulation of nuclear receptors in obesity-related metabolic syndrome. 1829 19

In prepubertal heifers, the mammary parenchyma consists of epithelial and myoepithelial cells growing within a mammary fat pad (MFP). The MFP produces IGF-I that stimulates epithelial cell proliferation. In other species, adipose tissue expansion induces inflammation-related proteins (IRP), such as tumor necrosis factor alpha (TNFalpha), interleukin (IL)-6, IL-1beta transforming growth factor beta, monocyte chemoattractant protein 1 (MCP-1), and plasminogen activator inhibitor-1 (PAI-1). The MFP production of IRP may influence mammary development because they impair not only insulin but also IGF-I actions. Moreover, the MFP expansion seen with development and increased nutrition coincides with reduced parenchymal growth. Our first objective was to identify IRP capable of altering proliferation of bovine mammary epithelial cells. TNFalpha, but neither IL-6, IL-1beta MCP-1 nor PAI-1, inhibited basal and IGF-I-stimulated proliferation in MAC-T cells and primary cells isolated from heifers. Our second objective was to determine whether MFP expression of IRP changed in a manner consistent with inhibition of parenchymal growth. MFP expression was measured from 100 to 350 kg body weight (experiment 1) or at 240 kg body weight (experiment 2) in dairy heifers offered restricted or high planes of nutrition. In experiment 1, neither nutrition nor development altered MFP expression of TNFalpha. Nutrition increased MCP-1 and PAI-1 but only before MFP expansion and after cessation of allometric parenchymal growth. In experiment 2, nutrition increased TNFalpha and PAI-1, but not MCP-1. Thus, MFP expansion increases IRP production in cattle, but this is unlikely to contribute to reduced parenchymal growth observed with development or increased nutrition.
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PMID:Regulation of mammary parenchymal growth by the fat pad in prepubertal dairy heifers: role of inflammation-related proteins. 1831 Apr 49

It is unclear whether an association between familial combined hyperlipidemia (FCHL) and inflammatory markers exists, independently of age, sex, body weight, insulin resistance, and metabolic syndrome. Serum concentrations of soluble vascular cell adhesion molecule-1 (sVCAM-1), monocyte chemoattractant protein 1, interleukin 6, tumor necrosis factor-alpha (TNF-alpha), and high-sensitive C-reactive protein were determined in 135 probands with FCHL and in 146 normolipidemic, normotensive, normoglycemic healthy subjects. Insulin resistance was evaluated using homeostasis model assessment (HOMA). All inflammatory parameters, except interleukin 6, were significantly higher in FCHL according to medians or mean comparisons. After adjustment for age, sex, body mass index, and HOMA, only TNF-alpha remained an independent predictor of FCHL status by binary logistic regression (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.07-1.31; P = .001). In particular, elevated levels of TNF-alpha (above the 90th and 95th percentiles of the value observed in the control group, 9.6 and 9.8 pg/mL, respectively) were independent predictors of FCHL status: for TNF-alpha above the 90th percentile, OR was 7.91 (95% CI, 3.27-19.13; P < .001), and for TNF-alpha above 95th percentile, OR was 13.08 (95% CI, 4.60-37.15; P < .0001). The independent role of TNF-alpha as predictor of FCHL status was confirmed after adjustment for components of the metabolic syndrome (P = .007 and P = .003, for TNF-alpha values above 90th and 95th percentiles, respectively). In conclusion, among the inflammatory markers most commonly measured, only TNF-alpha was associated with FCHL independently of age, sex, body mass index, and HOMA. The association of TNF-alpha with FCHL was also independent of the metabolic syndrome.
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PMID:Tumor necrosis factor-alpha is a marker of familial combined hyperlipidemia, independently of metabolic syndrome. 1832 61

In this study, we investigated the effects of the major green tea polyphenol, (-)-epigallocatechin-3-gallate (EGCG), on high-fat-induced obesity, symptoms of the metabolic syndrome, and fatty liver in mice. In mice fed a high-fat diet (60% energy as fat), supplementation with dietary EGCG treatment (3.2 g/kg diet) for 16 wk reduced body weight (BW) gain, percent body fat, and visceral fat weight (P < 0.05) compared with mice without EGCG treatment. The BW decrease was associated with increased fecal lipids in the high-fat-fed groups (r(2) = 0.521; P < 0.05). EGCG treatment attenuated insulin resistance, plasma cholesterol, and monocyte chemoattractant protein concentrations in high-fat-fed mice (P < 0.05). EGCG treatment also decreased liver weight, liver triglycerides, and plasma alanine aminotransferase concentrations in high-fat-fed mice (P < 0.05). Histological analyses of liver samples revealed decreased lipid accumulation in hepatocytes in mice treated with EGCG compared with high-fat diet-fed mice without EGCG treatment. In another experiment, 3-mo-old high-fat-induced obese mice receiving short-term EGCG treatment (3.2 g/kg diet, 4 wk) had decreased mesenteric fat weight and blood glucose compared with high-fat-fed control mice (P < 0.05). Our results indicate that long-term EGCG treatment attenuated the development of obesity, symptoms associated with the metabolic syndrome, and fatty liver. Short-term EGCG treatment appeared to reverse preexisting high-fat-induced metabolic pathologies in obese mice. These effects may be mediated by decreased lipid absorption, decreased inflammation, and other mechanisms.
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PMID:The major green tea polyphenol, (-)-epigallocatechin-3-gallate, inhibits obesity, metabolic syndrome, and fatty liver disease in high-fat-fed mice. 1871 69

Obesity is associated with a low-grade inflammation in adipose tissue resulting from increased production of pro-inflammatory cytokines and which can subsequently contribute to the development of insulin resistance. However, the mechanisms underlying the transcriptional regulation of pro-inflammatory genes are still unclear. Here we show that tumor necrosis factor (TNF)-alpha treatment attenuated Akt-dependent phosphorylation of Foxo1 and enhanced transcriptional activity of Foxo1. We found that Foxo1 increased the expression of CCAAT/enhancer binding protein (C/EBPbeta, a positive regulator of monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6 genes, through directly binding to its promoter. Furthermore, knockdown of Foxo1 as well as C/EBPbeta inhibits TNF-alpha-induced expression of MCP-1 and IL-6 in 3T3-L1 adipocytes. These findings suggest that activation of Foxo1 triggered by TNF-alpha up-regulates the expression of C/EBPbeta in 3T3-L1 adipocytes, thereby leading to an increased production of pro-inflammatory cytokines, MCP-1 and IL-6.
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PMID:Foxo1 increases pro-inflammatory gene expression by inducing C/EBPbeta in TNF-alpha-treated adipocytes. 1902 86

Nonalcoholic fatty liver disease (NAFLD) is emerging as the most common liver disease in industrialized countries. Thus, the discovery of food components that would ameliorate NAFLD is of interest. Various mushrooms have been used in folk medicine for the treatment of lifestyle diseases in eastern countries and several compounds that modulate immune system, lower blood lipid levels, inhibit tumor and viral action have been isolated from them. In this study, we tested whether feeding Panellus serotinus (Mukitake) to db/db mice protects them from hepatic injury. After 4 weeks of feeding, hepatomegaly, hepatic triglyceride accumulation and elevated hepatic injury markers in serum were markedly alleviated in Mukitake-fed db/db mice compared with control mice. These effects were partly attributable to the enhancement of lipolytic enzyme activity and the suppression of lipogenic enzyme activities due to the Mukitake diet. The severe hyperinsulinemia in control db/db mice tended to attenuate in Mukitake-fed mice due to an enhanced production of adiponectin, which improves insulin sensitivity. Moreover, production of monocyte chemoattractant protein 1 (MCP1), an inflammatory cytokine, was markedly suppressed by the Mukitake diet. In addition, water-soluble extracts of Mukitake powder showed an inhibitory effect on inhibitor of kappaB (IkappaB) kinase (IKK) beta, whose activation is required for nuclear factor kappaB (NFkappaB)-mediated inflammatory response. We speculate that the development and progression of NAFLD was prevented by the reduction of MCP1 production through the interference in the IKKbeta-NFkappaB signaling pathway in Mukitake-fed db/db mice.
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PMID:Mukitake mushroom (Panellus serotinus) alleviates nonalcoholic fatty liver disease through the suppression of monocyte chemoattractant protein 1 production in db/db mice. 1942 19


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