Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

Permana, Paska A.; Menge, Christopher W.; Reaven, Peter D.

doi:10.1016/j.bbrc.2006.01.012

Cited by 269 publications

(227 citation statements)

References 45 publications

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“…Permana et al demonstrated that the supernatant of unstimulated RAW264.7 cells could induce the expression of pro-inflammatory cytokines including MCP-1 and IL-6 in differentiated 3T3-LI adipocytes. 34) In our experiments, hypertrophic adipocytes were cultured with a supernatant of LPS-stimulated RAW264.7. We did not use the unstimulated supernatant as a control, instead using directly treated LPS in DMEM for comparison.…”

Section: Discussionmentioning

confidence: 99%

Caffeic Acid Phenethyl Ester Suppresses the Production of Pro-inflammatory Cytokines in Hypertrophic Adipocytes through Lipopolysaccharide-Stimulated Macrophages

Juman

Yasui

Ikeda

et al. 2012

Biological & Pharmaceutical Bulletin

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Obesity is a condition in which excess body fat accumulates due to lipids producing adipocytes and an increased number of differentiated mature cells. Recently, new findings have shown that macrophages infiltrate into adipose tissues and produce various pro-inflammatory cytokines in obese subjects. The inflammatory changes induced by the cross-talk between adipocytes and macrophages are critical for the pathophysiology of obesity and thus of metabolic syndrome. Caffeic acid phenethyl ester (CAPE) is known to have many functions, including antibacterial, anticancer and anti-inflammatory properties, but there is no evidence of its effect on the inflammatory responses in hypertrophic adipocytes through stimulation by macrophages. We investigated the effect of CAPE on macrophages and hypertrophic adipocytes in this study. CAPE significantly suppressed the levels of lipopolysaccharide (LPS)-induced interleukin (IL)-1-beta, tumor necrosis factor (TNF)-alpha and monocyte chemoattractant protein (MCP)-1 from a macrophage cell line, RAW264.7. Supernatants of stimulated RAW264.7 macrophages drastically increased mRNA levels of pro-inflammatory cytokines such as IL-6, MCP-1 and TNF-alpha in 3T3-L1 hypertrophic adipocytes. CAPE also significantly and dose-dependently reduced the gene expression of these cytokines. Our findings indicate that CAPE has inhibitory effects on the production of pro-inflammatory cytokines from LPS-stimulated RAW264.7 macrophages. In addition, CAPE suppressed gene expressions of cytokines under inflammatory conditions of hypertrophic adipocytes, suggesting that it may have the potential to suppress inflammation by macrophage infiltration into adipose tissue in obese patients.Key words caffeic acid phenethyl ester; hypertrophic adipocyte; macrophage; pro-inflammatory cytokine Obesity is a major risk factor for metabolic syndrome, which includes a number of disorders, such as hypertension, heart diseases and diabetes.1,2) Obesity is a condition in which excess body fat accumulates due to lipids producing hypertrophic adipocytes and an increased number of differentiated mature cells. This process is regulated by genetic and environmental factors, such as nutrient intake.3,4) It is known that adipocytes in obese individuals show cell hypertrophy and chronic inflammation. The inflammatory changes induced by the cross-talk between adipocytes and macrophages are critical for the pathophysiology of obesity and thus of metabolic syndrome. 5,6) Recent studies have demonstrated that obese adipose tissue is characterized by increased infiltration of macrophages, 7,8) which produce various inflammatory proteins. The inflammation process is associated with the activation of macrophages and the release of pro-inflammatory cytokines, such as interleukin (IL)-1-beta, tumor necrosis factor (TNF)-alpha, monocyte chemoattractant protein (MCP)-1 and interleukin (IL)-6. 9,10) MCP-1, known to play a pivotal role in macrophage trafficking and activation, is produced by macrophages and adipocytes. Several reports suggest t...

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Section: Discussionmentioning

confidence: 99%

Caffeic Acid Phenethyl Ester Suppresses the Production of Pro-inflammatory Cytokines in Hypertrophic Adipocytes through Lipopolysaccharide-Stimulated Macrophages

Juman

Yasui

Ikeda

et al. 2012

Biological & Pharmaceutical Bulletin

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“…[5][6][7][8] Since adipocyte function is an important factor for systemic insulin sensitivity, 9 ATMs appear to contribute critically to the pathogenesis of type 2 diabetes mellitus and the metabolic syndrome. However, molecular details underlying the insulin desensitizing effects of ATMs are unresolved yet, 10 since the nature of ATMs has remained largely unknown so far.…”

Section: Introductionmentioning

confidence: 99%

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

et al. 2007

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Objective: Obesity is associated with a chronic low-grade inflammation and an increased abundance of macrophages in adipose tissue. Adipose tissue macrophages (ATMs) are assumed to interfere with adipocyte function leading to insulin resistance, thereby contributing to the pathogenesis of type 2 diabetes mellitus. Macrophages exist in separate types of differentiation, but the nature of ATMs is largely unknown. Design and measurements: Stromal vascular cells (SVCs) and ATMs were isolated from human adipose tissues from different locations. We characterized ATMs phenotypically and functionally by flow cytometry, endocytosis assay and determination of secreted cytokines. For comparison, we used macrophages of the 'classical' (M1) and the 'alternative', anti-inflammatory (M2) type differentiated in vitro from peripheral blood monocytes. Results: Like prototypic M2 macrophages, ATMs expressed considerable amounts of mannose receptor, haemoglobin scavenger receptor CD163 and integrin avb5. The number of cells expressing these molecules correlated significantly with the donors' body mass indices (BMIs). Notably, SVCs positive for the common monocyte/macrophage marker CD14 contained a considerable fraction of blood monocytes, the abundance of which did not correlate with the BMIs, pointing to the requirement of the surface markers identified here for the identification of ATMs. ATMs showed endocytic activities similar to M2 macrophages and accordingly secreted high amounts of IL-10 and IL-1 receptor antagonist. However, basal and induced secretion of pro-inflammatory mediators TNF-a, IL-6, IL-1, MCP-1 and MIP-1a was even higher in ATMs than in proinflammatory M1 macrophages. Conclusion: ATMs comprise a particular macrophage type that is M2-like by surface marker expression, but they are competent to produce extensive amounts of inflammatory cytokines, which could considerably contribute to the development of insulin resistance.

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“…1) as follows: (1) dysregulation of the sympathetic nervous system causes obesity and dyslipidaemia [11]; (2) dysregulation of lipogenesis and lipoprotein metabolism causes ectopic fat deposition, dyslipidaemia, inflammation and insulin resistance [12][13][14][15]; (3) abnormalities in stress and natriuretic responses and vascular reactivity contribute to hypertension [16,17] Fig. 1 The first component of SEM comprises a factor analysis model, in which closely correlated measured variables (in rectangles) are loaded onto latent factors (in ovals) to give a more precise interpretation.…”

Section: Introductionmentioning

confidence: 99%

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

Song

Lee

et al. 2009

Diabetologia

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Aims/hypothesis Cardiovascular and renal diseases share common risk factors. We used structural equation modelling (SEM) to evaluate the independent and combined effects of phenotypes and genotypes implicated in cardiovascular diseases on renal function in type 2 diabetes.Methods 1,188 type 2 diabetic patients were stratified into high-risk and low-risk groups according to bimodal distributions of the logarithmically transformed (log e ) urinary albumin:creatinine ratio and plasma creatinine levels. Models for these groups, comprising continuous and non-ranking categorical data, were developed separately to evaluate the inter-relationships among measured variables and latent factors using non-linear SEMs, Bayesian estimation and model selection as assessed by a goodness-of-fit statistic. Results Inter-correlated measured variables (obesity, glycaemia, lipid, blood pressure) and variants of the genes encoding endothelial nitric oxide synthase (NOS), β-adrenergic receptor (ADRB), components of the reninangiotensin system (RAS) and lipid metabolism were loaded onto their respective latent factors of phenotypes and genotypes. In addition to direct and indirect effects, latent factors of obesity, lipid and BP interacted with latent factors of ADRB and RAS genotypes to influence renal function. Together with variants of the genes encoding peroxisome proliferator-activated receptor γ, atrial natriuretic peptide, adducin, G protein β 3 subunit, epithelial sodium channel α subunit and matrix metallopeptidase 3, these parameters explained 39-80% of the variance in renal function in the high-risk and low-risk models. Conclusions/interpretation SEM is a useful tool for confirming and quantifying multiple interactions of biological pathways with genetic determinants. The combined and interactive effects of blood pressure, lipid and obesity on renal function may have therapeutic implications, especially in type 2 diabetic individuals with genetic risk factors.

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Macrophage-secreted factors induce adipocyte inflammation and insulin resistance

Cited by 269 publications

References 45 publications

Caffeic Acid Phenethyl Ester Suppresses the Production of Pro-inflammatory Cytokines in Hypertrophic Adipocytes through Lipopolysaccharide-Stimulated Macrophages

Caffeic Acid Phenethyl Ester Suppresses the Production of Pro-inflammatory Cytokines in Hypertrophic Adipocytes through Lipopolysaccharide-Stimulated Macrophages

Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production

Phenotype–genotype interactions on renal function in type 2 diabetes: an analysis using structural equation modelling

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