scholarly journals Human Adipose Tissue Macrophages Are Enhanced but Changed to an Anti-Inflammatory Profile in Obesity

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Karen Fjeldborg ◽  
Steen B. Pedersen ◽  
Holger J. Møller ◽  
Tore Christiansen ◽  
Marianne Bennetzen ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Multivariate Regression Analysis ◽  
Low Grade ◽  
Macrophage Marker ◽  
Adipose Tissue Macrophages ◽  
Obese Subjects ◽  
Anti Inflammatory ◽  
Inflammatory Profile

Objective. Adipose tissue (AT) macrophages are increased in obesity and associated with low grade inflammation. We aimed to characterize the phenotype of AT macrophages in humans in relation to obesity and insulin resistance.Design. Gene-expression levels of general macrophage markers (CD68 and CD14), proinflammatory markers/M1 (TNF-α, MCP-1, and IL-6), and anti-inflammatory markers/M2 (CD163, CD206, and IL-10) were determined by RT-PCR in subcutaneous AT samples from lean and obese subjects. Insulin resistance was determined by HOMA-IR.Results. All the macrophage markers were elevated in the AT from obese compared to lean subjects (P<0.001). To determine the phenotype of the macrophages the level of CD14 was used to adjust the total number of macrophages. The relative expression of CD163 and IL-10 was elevated, and TNF-αand IL-6 were reduced in AT from obese subjects (allP<0.05). In a multivariate regression analysis CD163 was the only macrophage marker significantly associated with HOMA-IR (β: 0.57;P<0.05). Conclusion. Obesity is associated with elevated numbers of macrophages in the AT. Unexpectedly, the macrophages change phenotype by obesity, with a preponderance of M2 and a decrement of M1 markers in AT from obese subjects. Moreover, CD163 was the only macrophage marker associated with HOMA-IR after multiple adjustments.

scholarly journals Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation

2018 ◽  
Vol 51 (3) ◽  
pp. 1051-1068 ◽  
Author(s):  
Jèssica Latorre ◽  
José M. Moreno-Navarrete ◽  
Mónica Sabater ◽  
Maria Buxo ◽  
José I. Rodriguez-Hermosa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Inflammation ◽  
Fat Depots ◽  
Acute Surgery ◽  
Obese Subjects ◽  
Anti Inflammatory ◽  
The Impact

Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.

scholarly journals Adipose tissue macrophages in aging-associated adipose tissue function

2021 ◽  
Vol 71 (1) ◽  
Author(s):  
Bangchao Lu ◽  
Liang Huang ◽  
Juan Cao ◽  
Lingling Li ◽  
Wenhui Wu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Therapeutic Targets ◽  
Visceral Adiposity ◽  
Low Grade ◽  
Recent Advances ◽  
Adipose Tissue Macrophages ◽  
Low Grade Inflammation

Abstract“Inflammaging” refers to the chronic, low-grade inflammation that characterizes aging. Aging, like obesity, is associated with visceral adiposity and insulin resistance. Adipose tissue macrophages (ATMs) have played a major role in obesity-associated inflammation and insulin resistance. Macrophages are elevated in adipose tissue in aging. However, the changes and also possibly functions of ATMs in aging and aging-related diseases are unclear. In this review, we will summarize recent advances in research on the role of adipose tissue macrophages with aging-associated insulin resistance and discuss their potential therapeutic targets for preventing and treating aging and aging-related diseases.

scholarly journals Serum Resistin (FIZZ3) Protein Is Increased in Obese Humans

2003 ◽  
Vol 88 (11) ◽  
pp. 5452-5455 ◽  
Author(s):  
Mikako Degawa-Yamauchi ◽  
Jason E. Bovenkerk ◽  
Beth Elisa Juliar ◽  
William Watson ◽  
Kimberly Kerr ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Significant Positive Correlation ◽  
Human Adipose Tissue ◽  
Model Assessment ◽  
Homeostasis Model Assessment ◽  
Obese Subjects ◽  
Isolated Adipocytes ◽  
Resistance Score

Abstract The role of resistin in obesity and insulin resistance in humans is controversial. Therefore, resistin protein was quantitated by ELISA in serum of 27 lean [13 women/14 men, body mass index (BMI) 21.7 ± 0.4 kg/m2, age 33 ± 2 yr] and 50 obese (37 women/13 men, BMI 49.8 ± 1.5 kg/m2, age 47 ± 1 yr) subjects. There was more serum resistin protein in the obese (mean ± sem: 5.3 ± 0.4 ng/ml; range 1.8–17.9) than lean subjects (3.6 ± 0.4 ng/ml; range 1.5–9.9; P = 0.001). The elevation of serum resistin in obese humans was confirmed by Western blot as was expression of resistin protein in human adipose tissue and isolated adipocytes. There was a significant positive correlation between resistin and BMI (r = 0.37; P = 0.002). Multiple regression analysis with predictors BMI and resistin explained 25% of the variance in homeostasis model assessment of insulin resistance score. BMI was a significant predictor of insulin resistance (P = 0.0002), but resistin adjusted for BMI was not (P = 0.11). The data demonstrate that resistin protein is present in human adipose tissue and blood, and that there is significantly more resistin in the serum of obese subjects. Serum resistin is not a significant predictor of insulin resistance in humans.

2094-P: Decreased Human Adipose Tissue-Resident Eosinophils in Obese Subjects Is Associated with Increased Insulin Resistance

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 2094-P ◽  
Author(s):  
JAMES D. HERNANDEZ ◽  
TING LI ◽  
CASSANDRA RAU ◽  
MIA Y. MASUDA ◽  
JAMES A. MADURA ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Obese Subjects

scholarly journals Identification of Three Significant Genes Associated with Immune Cells Infiltration in Dysfunctional Adipose Tissue-Induced Insulin-Resistance of Obese Patients via Comprehensive Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Ming Zhai ◽  
Peipei Luan ◽  
Yefei Shi ◽  
Bo Li ◽  
Jianhua Kang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Correlation Analysis ◽  
Immune Cells ◽  
Plasma Cells ◽  
Immune Cell ◽  
Low Grade ◽  
Hub Genes ◽  
Bioinformatics Analyses ◽  
Adipose Tissue Macrophages

Background. Low-grade chronic inflammation in dysfunctional adipose tissue links obesity with insulin resistance through the activation of tissue-infiltrating immune cells. Numerous studies have reported on the pathogenesis of insulin-resistance. However, few studies focused on genes from genomic database. In this study, we would like to explore the correlation of genes and immune cells infiltration in adipose tissue via comprehensive bioinformatics analyses and experimental validation in mice and human adipose tissue. Methods. Gene Expression Omnibus (GEO) datasets (GSE27951, GSE55200, and GSE26637) of insulin-resistant individuals or type 2 diabetes patients and normal controls were downloaded to get differently expressed genes (DEGs), and GO and KEGG pathway analyses were performed. Subsequently, we integrated DEGs from three datasets and constructed commonly expressed DEGs’ PPI net-works across datasets. Center regulating module of DEGs and hub genes were screened through MCODE and cytoHubba in Cytoscape. Three most significant hub genes were further analyzed by GSEA analysis. Moreover, we verified the predicted hub genes by performing RT qPCR analysis in animals and human samples. Besides, the relative fraction of 22 immune cell types in adipose tissue was detected by using the deconvolution algorithm of CIBERSORT (Cell Type Identification by Estimating Relative Subsets of RNA Transcripts). Furthermore, based on the significantly changed types of immune cells, we performed correlation analysis between hub genes and immune cells. And, we performed immunohistochemistry and immunofluorescence analysis to verify that the hub genes were associated with adipose tissue macrophages (ATM). Results. Thirty DEGs were commonly expressed across three datasets, most of which were upregulated. DEGs mainly participated in the process of multiple immune cells’ infiltration. In protein-protein interaction network, we identified CSF1R, C1QC, and TYROBP as hub genes. GSEA analysis suggested high expression of the three hub genes was correlated with immune cells functional pathway’s activation. Immune cell infiltration and correlation analysis revealed that there were significant positive correlations between TYROBP and M0 macrophages, CSF1R and M0 macrophages, Plasma cells, and CD8 T cells. Finally, hub genes were associated with ATMs infiltration by experimental verification. Conclusions. This article revealed that CSF1R, C1QC, and TYROBP were potential hub genes associated with immune cells’ infiltration and the function of proinflammation, especially adipose tissue macrophages, in the progression of obesity-induced diabetes or insulin-resistance.

scholarly journals Adipokine inflammation and insulin resistance: the role of glucose, lipids and endotoxin

2012 ◽  
Vol 216 (1) ◽  
pp. T1-T15 ◽  
Author(s):  
M K Piya ◽  
P G McTernan ◽  
S Kumar
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Dietary Factors ◽  
Positive Energy ◽  
Low Grade ◽  
Positive Energy Balance ◽  
Secretory Tissue ◽  
The Impact ◽  
Low Grade Inflammation

Adipose tissue is an active endocrine organ, and our knowledge of this secretory tissue, in recent years, has led us to completely rethink how our body functions and becomes dysregulated with weight gain. Human adipose tissue appears to act as a multifunctional secretory organ with the capacity to control energy homoeostasis through peripheral and central regulation of energy homoeostasis. It also plays an important role in innate immunity. However, the capability to more than double its original mass to cope with positive energy balance in obesity leads to many pathogenic changes. These changes arise within the adipose tissue as well as inducing secondary detrimental effects on other organs like muscle and liver, including chronic low-grade inflammation mediated by adipocytokines (adipokine inflammation). This inflammation is modulated by dietary factors and nutrients including glucose and lipids, as well as gut bacteria in the form of endotoxin or LPS. The aim of this current review is to consider the impact of nutrients such as glucose and lipids on inflammatory pathways, specifically within adipose tissue. Furthermore, how nutrients such as these can influence adipokine inflammation and consequently insulin resistance directly through their effects on secretion of adipocytokines (TNFα, IL6 and resistin) as well as indirectly through increases in endotoxin is discussed.

scholarly journals Follistatin-Like 1: A Potential Mediator of Inflammation in Obesity

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Nengguang Fan ◽  
Haiyan Sun ◽  
Yufan Wang ◽  
Yifei Wang ◽  
Lijuan Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Low Grade ◽  
Dependent Manner ◽  
Proinflammatory Mediators ◽  
Raw264.7 Macrophages ◽  
Potential Mediator ◽  
Obese Subjects

Obesity is associated with a state of chronic low-grade inflammation, which contributes to insulin resistance and type 2 diabetes. However, the molecular mechanisms that link obesity to inflammation are not fully understood. Follistatin-like 1 (FSTL1) is a novel proinflammatory cytokine that is expressed in adipose tissue and secreted by preadipocytes/adipocytes. We aimed to test whether FSTL1 could have a role in obesity-induced inflammation and insulin resistance. It was found that FSTL1 expression was markedly decreased during differentiation of 3T3-L1 preadipocytes but reinduced by TNF-α. Furthermore, a significant increase in FSTL1 levels was observed in adipose tissue of obese ob/ob mice, as well as in serum of overweight/obese subjects. Mechanistic studies revealed that FSTL1 induced inflammatory responses in both 3T3-L1 adipocytes and RAW264.7 macrophages. The expression of proinflammatory mediators including IL-6, TNF-α, and MCP-1 was upregulated by recombinant FSTL1 in a dose-dependent manner, paralleled with activation of the IKKβ-NFκB and JNK signaling pathways in the two cell lines. Moreover, FSTL1 impaired insulin signaling in 3T3-L1 adipocytes, as revealed by attenuated phosphorylation of both Akt and IRS-1 in response to insulin stimulation. Together, our results suggest that FSTL1 is a potential mediator of inflammation and insulin resistance in obesity.

Abstract 700: Accelerated Glycolysis in Adipose Tissue Macrophages Triggers Hif-1α in Obesity and Promotes Insulin Resistance.

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Bhama Ramkhelawon ◽  
Mireille Ouimet ◽  
Russell Simon ◽  
Bo Yan ◽  
Westley Spiro ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Flux Analysis ◽  
Low Grade ◽  
Metabolic Dysfunction ◽  
Knock Out ◽  
Extracellular Flux ◽  
Adipose Tissue Macrophages ◽  
Knock Out Mice

During obesity, macrophages (Mø) accumulate in the visceral adipose tissue (VAT), giving rise to a state of chronic, low-grade inflammation that promotes insulin resistance and type 2 diabetes. We hypothesized that activation of HIF-1α in highly-metabolically active Mø sustains inflammation in obese VAT and promotes metabolic dysfunction. We show that hypoxic Mø, like M1-polarized Mø, shift their metabolism from oxidative phosphorylation to glycolysis, leading to the accumulation of HIF-1α-stabilizing intermediates. Extracellular flux analysis showed that treating Mø with the hypoxia mimetic CoCl2 or the saturated fatty acid palmitate reduced cellular oxygen consumption and increased the rate of extracellular acidification indicative of enhanced glycolysis. Metabolites known to accumulate during persistent glycolysis, such as succinate and lactic acid, activated HIF-1α in Mø and promoted inflammatory gene expression. To test the role of Mø HIF-1α in promoting VAT inflammation and metabolic dysfunction in obesity, we fed wild type or Mø-specific HIF-1α knock-out mice a high-fat diet (60% kcal fat) for 20 weeks. Notably, the ablation of HIF-1α in Mø reduced VAT inflammation as indicated by the reduced accumulation of F4/80+ cells and decreased expression of inflammatory cytokines (TNFα, IL-6, MCP-1). In addition, adipose tissue Mø isolated from Mø-HIF-1α knock-out mice showed increased expression of markers characteristic of M2 reparative Mø (Ym1, Fizz1, Aldh2) and reduced expression of M1 inflammatory Mø markers (Ccl2, Il1b), compared to Mø from WT mice. Furthermore, Mø-HIF-1α knock-out mice showed improved glucose homeostasis and insulin sensitivity, and reduced plasma insulin and free fatty acid levels compared to WT mice. Together, these data indicate that activation of HIF-1α in VAT Mø during obesity promotes tissue inflammation and insulin resistance.

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