scholarly journals CREB pathway links PGE2 signaling with macrophage polarization

2015 ◽  
Vol 112 (51) ◽  
pp. 15642-15647 ◽  
Author(s):  
Bing Luan ◽  
Young-Sil Yoon ◽  
John Le Lay ◽  
Klaus H. Kaestner ◽  
Susan Hedrick ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune System ◽  
Insulin Sensitivity ◽  
Innate Immune System ◽  
Marker Gene ◽  
Innate Immune ◽  
M2 Polarization ◽  
Marker Gene Expression

Obesity is thought to promote insulin resistance in part via activation of the innate immune system. Increases in proinflammatory cytokine production by M1 macrophages inhibit insulin signaling in white adipose tissue. In contrast, M2 macrophages have been found to enhance insulin sensitivity in part by reducing adipose tissue inflammation. The paracrine hormone prostaglandin E2 (PGE2) enhances M2 polarization in part through activation of the cAMP pathway, although the underlying mechanism is unclear. Here we show that PGE2 stimulates M2 polarization via the cyclic AMP-responsive element binding (CREB)-mediated induction of Krupple-like factor 4 (KLF4). Targeted disruption of CREB or the cAMP-regulated transcriptional coactivators 2 and 3 (CRTC2/3) in macrophages down-regulated M2 marker gene expression and promoted insulin resistance in the context of high-fat diet feeding. As re-expression of KLF4 rescued M2 marker gene expression in CREB-depleted cells, our results demonstrate the importance of the CREB/CRTC pathway in maintaining insulin sensitivity in white adipose tissue via its effects on the innate immune system.

scholarly journals The Role of the Immune System in Obesity and Insulin Resistance

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Payal S. Patel ◽  
Eric D. Buras ◽  
Ashok Balasubramanyam
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Immune System ◽  
Stress Responses ◽  
Innate Immune System ◽  
Metabolic Diseases ◽  
Innate Immune ◽  
Metabolic Dysfunction ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation

The innate immune system provides organisms with rapid and well-coordinated protection from foreign pathogens. However, under certain conditions of metabolic dysfunction, components of the innate immune system may be activated in the absence of external pathogens, leading to pathologic consequences. Indeed, there appears to be an intimate relationship between metabolic diseases and immune dysfunction; for example, macrophages are prime players in the initiation of a chronic inflammatory state in obesity which leads to insulin resistance. In response to increases in free fatty acid release from obese adipose depots, M1-polarized macrophages infiltrate adipose tissues. These M1 macrophages trigger inflammatory signaling and stress responses within cells that signal through JNK or IKKβpathways, leading to insulin resistance. If overnutrition persists, mechanisms that counteract inflammation (such as M2 macrophages and PPAR signaling) are suppressed, and the inflammation becomes chronic. Although macrophages are a principal constituent of obese adipose tissue inflammation, other components of the immune system such as lymphocytes and mast cells also contribute to the inflammatory cascade. Thus it is not merely an increased mass of adipose tissue that directly leads to attenuation of insulin action, but rather adipose tissue inflammation activated by the immune system in obese individuals that leads to insulin resistance.

scholarly journals Gene expression analysis of the innate immune system during early rearing and weaning of meagre (Argyrosomus regius)

2019 ◽  
Vol 94 ◽  
pp. 819-832
Author(s):  
Cindy Campoverde ◽  
Douglas J. Milne ◽  
Christopher J. Secombes ◽  
Alicia Estévez ◽  
Enric Gisbert ◽  
...  
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Expression Analysis ◽  
Innate Immune System ◽  
Gene Expression Analysis ◽  
Innate Immune ◽  
Argyrosomus Regius ◽  
Early Rearing

scholarly journals Candidate innate immune system gene expression in the ecological model Daphnia

2011 ◽  
Vol 35 (10) ◽  
pp. 1068-1077 ◽  
Author(s):  
Ellen Decaestecker ◽  
Pierrick Labbé ◽  
Kirsten Ellegaard ◽  
Judith E. Allen ◽  
Tom J. Little
Keyword(s):  
Gene Expression ◽  
Immune System ◽  
Innate Immune System ◽  
Ecological Model ◽  
Innate Immune

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

scholarly journals Stress Hyperglycemia, Insulin Treatment, and Innate Immune Cells

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Fangming Xiu ◽  
Mile Stanojcic ◽  
Li Diao ◽  
Marc G. Jeschke
Keyword(s):  
Insulin Resistance ◽  
Innate Immunity ◽  
Immune System ◽  
Critical Illness ◽  
Immune Cells ◽  
Innate Immune System ◽  
Insulin Treatment ◽  
Innate Immune ◽  
Morbidity And Mortality ◽  
Innate Immune Cells

Hyperglycemia (HG) and insulin resistance are the hallmarks of a profoundly altered metabolism in critical illness resulting from the release of cortisol, catecholamines, and cytokines, as well as glucagon and growth hormone. Recent studies have proposed a fundamental role of the immune system towards the development of insulin resistance in traumatic patients. A comprehensive review of published literatures on the effects of hyperglycemia and insulin on innate immunity in critical illness was conducted. This review explored the interaction between the innate immune system and trauma-induced hypermetabolism, while providing greater insight into unraveling the relationship between innate immune cells and hyperglycemia. Critical illness substantially disturbs glucose metabolism resulting in a state of hyperglycemia. Alterations in glucose and insulin regulation affect the immune function of cellular components comprising the innate immunity system. Innate immune system dysfunction via hyperglycemia is associated with a higher morbidity and mortality in critical illness. Along with others, we hypothesize that reduction in morbidity and mortality observed in patients receiving insulin treatment is partially due to its effect on the attenuation of the immune response. However, there still remains substantial controversy regarding moderate versus intensive insulin treatment. Future studies need to determine the integrated effects of HG and insulin on the regulation of innate immunity in order to provide more effective insulin treatment regimen for these patients.

Inflammation of the cystic fibrosis mouse small intestine

2004 ◽  
Vol 286 (6) ◽  
pp. G1032-G1041 ◽  
Author(s):  
Oxana Norkina ◽  
Simran Kaur ◽  
Donna Ziemer ◽  
Robert C. De Lisle
Keyword(s):  
Gene Expression ◽  
Cystic Fibrosis ◽  
Small Intestine ◽  
Immune System ◽  
Mast Cells ◽  
Innate Immune System ◽  
Innate Immune ◽  
Serum Amyloid ◽  
Mouse Small Intestine ◽  
Cytochrome P 450

The CFTR null mouse [cystic fibrosis (CF) mouse] has a severe intestinal phenotype that serves as a model for CF-related growth deficiency, meconium ileus, and distal intestinal obstructive syndrome. DNA microarray analysis was used to investigate gene expression in the CF mouse small intestine. Sixty-one genes exhibited a statistically significant twofold or greater increase in expression, and 98 genes were downregulated twofold or greater. Of the upregulated genes, most were associated with inflammation and included markers for cells of the innate immune system (mast cells and neutrophils) and for acute-phase genes (serum amyloid A and complement factors). The downregulated genes include 10 cytochrome P-450 genes; several are involved in lipid metabolism, and several are involved in various transport processes. Confirmation by quantitative RT-PCR showed gene expression was significantly increased for mast cell protease 2 (27-fold), hematopoietic cell transcript 1 (17-fold), serum amyloid A3 (2.9-fold), suppressor of cytokine signaling 3 (2.0-fold), leucine-rich α2-glycoprotein (21-fold), resistin-like molecule-β (49-fold), and Muclin (2.5-fold) and was significantly decreased for cytochrome P-450 4a10 (28-fold) and cubilin (114-fold). Immune cell infiltration was confirmed histologically by staining for mast cells and neutrophils. These data demonstrate that the CF intestine exhibits an inflammatory state with upregulation of components of the innate immune system.

Acute-phase responses and adipocytokines

2013 ◽  
Author(s):  
Elena Neumann ◽  
Klaus Frommer ◽  
Ulf Müller-Ladner
Keyword(s):  
Adipose Tissue ◽  
Immune System ◽  
Chronic Inflammation ◽  
Acute Phase ◽  
Innate Immune System ◽  
Current Knowledge ◽  
Cell Types ◽  
Innate Immune ◽  
Bioactive Substances ◽  
Different Cell Types

Adipokines, also called adipocytokines, are highly bioactive substances mainly expressed by adipose tissue. In addition to adipocytes, different cell types resident in various tissues produce adipokines under pathophysiological conditions. Adipokines include a growing number of pluripotent molecules such as adiponectin, resistin, leptin, and visfatin. Since distinct effects of adipokines on inflammation have been described, their influence on the (innate) immune system has been investigated in rheumatology, gastroenterology, and endocrinology. This review gives an overview on the current knowledge about the influence which adipokines have on the immune system and chronic inflammation in rheumatic diseases.

scholarly journals Dynamic Strength Training Improves Insulin Sensitivity without Altering Plasma Levels and Gene Expression of Adipokines in Subcutaneous Adipose Tissue in Obese Men

2006 ◽  
Vol 91 (12) ◽  
pp. 5107-5112 ◽  
Author(s):  
E. Klimcakova ◽  
J. Polak ◽  
C. Moro ◽  
J. Hejnova ◽  
M. Majercik ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Strength Training ◽  
Plasma Levels ◽  
Dynamic Strength ◽  
Whole Body ◽  
Obese Subjects ◽  
Dynamic Strength Training

Abstract Context: Obesity is characterized by a low-grade inflammatory state, which could play a role in insulin resistance. Dynamic strength training improves insulin sensitivity. Objective: The objective of this study was to investigate, in obese subjects, whether the insulin sensitizing effect of dynamic strength training is associated with changes in plasma levels and gene expression of adipokines potentially involved in the development of insulin resistance. Design: Twelve obese male subjects were investigated before and at the end of 3 months of dynamic strength training. Insulin sensitivity was evaluated using euglycemic-hyperinsulinemic clamp. Blood samples and needle biopsy samples of sc abdominal adipose tissue were obtained. The plasma levels and adipose tissue mRNA levels of adiponectin, leptin, IL-1β, IL-6, and TNF-α were determined. Results: The training induced an increase in the whole-body glucose disposal rate by 24% (P = 0.04). The body weight was not altered during the training. Plasma levels of leptin decreased during the training (16.6 ± 6.3 vs. 13.1 ± 5.7 ng/ml) by 21% (P &lt; 0.02), whereas no change in plasma levels of other adipokines and C-reactive protein was observed. Gene expression of the investigated adipokines was not changed in sc adipose tissue during the training. Conclusions: In obese subjects, the dynamic strength training resulted in an improvement of whole-body insulin sensitivity. The increase in insulin sensitivity was not associated with training-induced modifications of plasma levels or adipose tissue gene expression of adipokines supposedly involved in the development of insulin resistance.

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