scholarly journals Estrogen Signaling in Metabolic Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Rosário Monteiro ◽  
Diana Teixeira ◽  
Conceição Calhau

There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Faloia Emanuela ◽  
Michetti Grazia ◽  
De Robertis Marco ◽  
Luconi Maria Paola ◽  
Furlani Giorgio ◽  
...  

The metabolic syndrome is a complex of clinical features leading to an increased risk for cardiovascular disease and type 2 diabetes mellitus in both sexes. Visceral obesity and insulin resistance are considered the main features determining the negative cardiovascular profile in metabolic syndrome. The aim of this paper is to highlight the central role of obesity in the development of a chronic low-grade inflammatory state that leads to insulin resistance, endothelial and microvascular dysfunctions. It is thought that the starting signal of this inflammation is overfeeding and the pathway origins in all the metabolic cells; the subsequent increase in cytokine production recruits immune cells in the extracellular environment inducing an overall systemic inflammation. This paper focuses on the molecular and cellular inflammatory mechanisms studied until now.


2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Masato Furuhashi ◽  
Shutaro Ishimura ◽  
Hideki Ota ◽  
Tetsuji Miura

Over the past decade, a large body of evidence has emerged demonstrating an integration of metabolic and immune response pathways. It is now clear that obesity and associated disorders such as insulin resistance and type 2 diabetes are associated with a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation.” Several inflammatory cytokines as well as lipids and metabolic stress pathways can activate metaflammation, which targets metabolically critical organs and tissues including adipocytes and macrophages to adversely affect systemic homeostasis. On the other hand, inside the cell, fatty acid-binding proteins (FABPs), a family of lipid chaperones, as well as endoplasmic reticulum (ER) stress, and reactive oxygen species derived from mitochondria play significant roles in promotion of metabolically triggered inflammation. Here, we discuss the molecular and cellular basis of the roles of FABPs, especially FABP4 and FABP5, in metaflammation and related diseases including obesity, diabetes, and atherosclerosis.


2020 ◽  
Vol 21 (23) ◽  
pp. 9005
Author(s):  
Nour-Mounira Z. Bakkar ◽  
Haneen S. Dwaib ◽  
Souha Fares ◽  
Ali H. Eid ◽  
Yusra Al-Dhaheri ◽  
...  

Cardiac autonomic neuropathy (CAN) is one of the earliest complications of type 2 diabetes (T2D), presenting a silent cause of cardiovascular morbidity and mortality. Recent research relates the pathogenesis of cardiovascular disease in T2D to an ensuing chronic, low-grade proinflammatory and pro-oxidative environment, being the hallmark of the metabolic syndrome. Metabolic inflammation emerges as adipose tissue inflammatory changes extending systemically, on the advent of hyperglycemia, to reach central regions of the brain. In light of changes in glucose and insulin homeostasis, dysbiosis or alteration of the gut microbiome (GM) emerges, further contributing to inflammatory processes through increased gut and blood–brain barrier permeability. Interestingly, studies reveal that the determinants of oxidative stress and inflammation progression exist at the crossroad of CAN manifestations, dictating their evolution along the natural course of T2D development. Indeed, sympathetic and parasympathetic deterioration was shown to correlate with markers of adipose, vascular, and systemic inflammation. Additionally, evidence points out that dysbiosis could promote a sympatho-excitatory state through differentially affecting the secretion of hormones and neuromodulators, such as norepinephrine, serotonin, and γ-aminobutyric acid, and acting along the renin–angiotensin–aldosterone axis. Emerging neuronal inflammation and concomitant autophagic defects in brainstem nuclei were described as possible underlying mechanisms of CAN in experimental models of metabolic syndrome and T2D. Drugs with anti-inflammatory characteristics provide potential avenues for targeting pathways involved in CAN initiation and progression. The aim of this review is to delineate the etiology of CAN in the context of a metabolic disorder characterized by elevated oxidative and inflammatory load.


2017 ◽  
Vol 8 (5) ◽  
pp. 529-540 ◽  
Author(s):  
S. A. Segovia ◽  
M. H. Vickers ◽  
C. M. Reynolds

Obesity is a global epidemic, affecting both developed and developing countries. The related metabolic consequences that arise from being overweight or obese are a paramount global health concern, and represent a significant burden on healthcare systems. Furthermore, being overweight or obese during pregnancy increases the risk of offspring developing obesity and other related metabolic complications in later life, which can therefore perpetuate a transgenerational cycle of obesity. Obesity is associated with a chronic state of low-grade metabolic inflammation. However, the role of maternal obesity-mediated alterations in inflammatory processes as a mechanism underpinning developmental programming in offspring is less understood. Further, the use of anti-inflammatory agents as an intervention strategy to ameliorate or reverse the impact of adverse developmental programming in the setting of maternal obesity has not been well studied. This review will discuss the impact of maternal obesity on key inflammatory pathways, impact on pregnancy and offspring outcomes, potential mechanisms and avenues for intervention.


2016 ◽  
Vol 7 (2) ◽  
pp. 181-194 ◽  
Author(s):  
R. Nagpal ◽  
M. Kumar ◽  
A.K. Yadav ◽  
R. Hemalatha ◽  
H. Yadav ◽  
...  

In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.


2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Caroline Maria Oliveira Volpe ◽  
Luana Farnese Machado Abreu ◽  
Pollyanna Stephanie Gomes ◽  
Raquel Miranda Gonzaga ◽  
Clara Araújo Veloso ◽  
...  

We examined nitric oxide (NO), IL-6, and TNF-αsecretion from cultured palmitate-stimulated PBMNCs or in the plasma from type 2 diabetes mellitus (T2MD) patients or nondiabetic (ND) controls. Free fatty acids (FFA) have been suggested to induce chronic low-grade inflammation, activate the innate immune system, and cause deleterious effects on vascular cells and other tissues through inflammatory processes. The levels of NO, IL-6, TNF-α, and MDA were higher in supernatant of palmitate stimulated blood cells (PBMNC) or from plasma from patients. The results obtained in the present study demonstrated that hyperglycemia in diabetes exacerbatesin vitroinflammatory responses in PBMNCs stimulated with high levels of SFA (palmitate). These results suggest that hyperglycemia primes PBMNCs for NO, IL-6, and TNF-alpha secretion underin vitroFFA stimulation are associated with the secretion of inflammatory biomarkers in diabetes. A combined therapy targeting signaling pathways activated by hyperglycemia in conjunction with simultaneous control of hyperglycemia and hypertriglyceridemia would be suggested for controlling the progress of diabetic complications.


2018 ◽  
Vol 45 (2) ◽  
pp. 572-590 ◽  
Author(s):  
Sardar Sindhu ◽  
Nadeem Akhter ◽  
Shihab Kochumon ◽  
Reeby Thomas ◽  
Ajit Wilson ◽  
...  

Background/Aims: Metabolic diseases such as obesity and type-2 diabetes (T2D) are known to be associated with chronic low-grade inflammation called metabolic inflammation together with an oxidative stress milieu found in the expanding adipose tissue. The innate immune Toll-like receptors (TLR) such as TLR2 and TLR4 have emerged as key players in metabolic inflammation; nonetheless, TLR10 expression in the adipose tissue and its significance in obesity/T2D remain unclear. Methods: TLR10 gene expression was determined in the adipose tissue samples from healthy non-diabetic and T2D individuals, 13 each, using real-time RT-PCR. TLR10 protein expression was determined by immunohistochemistry, confocal microscopy, and flow cytometry. Regarding in vitro studies, THP-1 cells, peripheral blood mononuclear cells (PBMC), or primary monocytes were treated with hydrogen peroxide (H2O2) for induction of reactive oxygen species (ROS)-mediated oxidative stress. Superoxide dismutase (SOD) activity was measured using a commercial kit. Data (mean±SEM) were compared using unpaired student’s t-test and P<0.05 was considered significant. Results: The adipose tissue TLR10 gene/protein expression was found to be significantly upregulated in obesity as well as T2D which correlated with body mass index (BMI). ROS-mediated oxidative stress induced high levels of TLR10 gene/protein expression in monocytic cells and PBMC. In these cells, oxidative stress induced a time-dependent increase in SOD activity. Pre-treatment of cells with anti-oxidants/ROS scavengers diminished the expression of TLR10. ROS-induced TLR10 expression involved the nuclear factor-kappaB (NF-κB)/mitogen activated protein kinase (MAPK) signaling as well as endoplasmic reticulum (ER) stress. H2O2-induced oxidative stress interacted synergistically with palmitate to trigger the expression of TLR10 which associated with enhanced expression of proinflammatory cytokines/chemokine. Conclusion: Oxidative stress induces the expression of TLR10 which may represent an immune marker for metabolic inflammation.


Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2224 ◽  
Author(s):  
Alina Kuryłowicz ◽  
Krzysztof Koźniewski

One of the concepts explaining the coincidence of obesity and type 2 diabetes (T2D) is the metaflammation theory. This chronic, low-grade inflammatory state originating from metabolic cells in response to excess nutrients, contributes to the development of T2D by increasing insulin resistance in peripheral tissues (mainly in the liver, muscles, and adipose tissue) and by targeting pancreatic islets and in this way impairing insulin secretion. Given the role of this not related to infection inflammation in the development of both: insulin resistance and insulitis, anti-inflammatory strategies could be helpful not only to control T2D symptoms but also to treat its causes. This review presents current concepts regarding the role of metaflammation in the development of T2D in obese individuals as well as data concerning possible application of different anti-inflammatory strategies (including lifestyle interventions, the extra-glycemic potential of classical antidiabetic compounds, nonsteroidal anti-inflammatory drugs, immunomodulatory therapies, and bariatric surgery) in the management of T2D.


2018 ◽  
Vol 2018 ◽  
pp. 1-18 ◽  
Author(s):  
Alex S. Yamashita ◽  
Thiago Belchior ◽  
Fábio S. Lira ◽  
Nicolette C. Bishop ◽  
Barbara Wessner ◽  
...  

Visceral obesity is frequently associated with the development of type 2 diabetes (T2D), a highly prevalent chronic disease that features insulin resistance and pancreatic β-cell dysfunction as important hallmarks. Recent evidence indicates that the chronic, low-grade inflammation commonly associated with visceral obesity plays a major role connecting the excessive visceral fat deposition with the development of insulin resistance and pancreatic β-cell dysfunction. Herein, we review the mechanisms by which nutrients modulate obesity-associated inflammation.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 499.1-499
Author(s):  
P. Falsetti ◽  
E. Conticini ◽  
C. Baldi ◽  
M. Bardelli ◽  
S. Gentileschi ◽  
...  

Background:Metabolic syndrome (MS) is a clinical condition characterized by central obesity and additional factors such dyslipidemia, hypertension, raised fasting plasma. Scanty observations describe the association of MS with musculoskeletal conditions, such as enthesopathies and diffuse idiopathic hyperostosis syndrome (DISH). Musculoskeletal ultrasound (US) has been applied to the study of entheses, but the real prevalence and characteristics of entheseal involvement in MS has yet to be clarified.Objectives:The aim of our work was to study the US-defined entheseal changes in MS, to correlates the US enthesitis scores to clinical characteristics, and to define a relation between MS-related enthesitis and the presence of concurrent DISHMethods:Sixty consecutive outpatients (24 males, 36 females, mean age 60 years), all fullfilling International Diabetes Foundation (IDF) criteria for MS, were also evaluated with multi-site bilateral US entheseal examination. Each patient underwent power Doppler (PD) US examination of twelve entheseal sites, using Esaote MyLab Twice with 6–18 MHz transducer. Enthesitis was defined on the basis of OMERACT’s filter. Inflammatory and structural changes were scored as a whole when present (score 1) or absent (score 0). The sum of entheses with inflammatory and structural damage was defined as “global inflammatory score” (GIs) and “global structural damage score” (GSDs) for each patient. The Leeds Enthesitis Index (LEI) was also applied, and a spinal radiography was obtained for each patient to research concurrent signs of DISH satisfying Resnick and Niwayama criteria.Results:Patients showed moderate overweight (mean BMI 29) and a diagnosis of type 2 diabetes was present in 24 (40%). A low-grade inflammatory state was demonstrated in MS (mean CRP 0,58 md/dL, mean ESR 21,9 mm/h). A high prevalence of US-defined enthesitis was noted in 52 patients (86%) and 127/720 entheses (17,6%). PD signals, were reported in 11 patients (18%) and 11/720 entheses (1,52%), and they were associated to clinical symptoms expressed as LEI (p=0,0138). Erosions, although rare (0.3% of entheses), were more frequent in males (p= 0.001). Moreover, in 57 patients (95%) and 217 entheses (30%) structural damages were found. A correlation was found between GIs and GSDs and both BMI (p=0.0233 and p=0.0068 respectively), LEI (p=0.03 and p=0.0099 respectively), and type 2 diabetes (p=0.0248 and p=0.0156 respectively). In 28 patients (46%) a concurrent diagnosis of DISH was made. In multivariate regression analysis the best predictors for DISH were higher levels of CRP (p=0,038) and older age (p<0,0001). DISH correlated with older age (p<0,0001), CRP and ESR (p= 0,0428 p=0,0069 respectively) and US global scores for enthesitis (p=0,0312 for GIs, p=0,0071 for GSDs).Conclusion:This is the first study where diffuse enthesitis and entheseal structural damage are demonstrated with high prevalences in MS, comparable or also higher than those reported for SpA-related enthesitis. Our data, obtained using the most recent OMERACT’s definition for US-detected enthesitis (proposed for SpA), also suggest a low specificity of this definition, in consideration of the high prevalence of MS-associated enthesitis. Moreover PD was associated to entheseal pain expressed as LEI. Both GIs and GSDs showed a correlation with overweight and type 2 diabetes. As secondary result, this study demonstrated that almost half of patients with MS could have a concurrent diagnosis of DISH. Patients with DISH were older, with higher levels of inflammation, and higher scores of US-defined enthesitis. Our results suggest that MS and DISH could be strictly related; diffuse enthesitis with a low-grade inflammatory state should be regarded as potential factor of progression from MS towards a conclamed DISH.Disclosure of Interests:None declared


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