scholarly journals Cellular hypoxia and adipose tissue dysfunction in obesity

2009 ◽  
Vol 68 (4) ◽  
pp. 370-377 ◽  
Author(s):  
I. Stuart Wood ◽  
Fátima Pérez de Heredia ◽  
Bohan Wang ◽  
Paul Trayhurn
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Strong Support ◽  
Low Grade ◽  
Tissue Mass ◽  
Diverse Range ◽  
Monocyte Chemoattractant Protein 1 ◽  
The Metabolic Syndrome ◽  
Adipose Tissue Dysfunction ◽  
Cellular Hypoxia

Expansion of adipose tissue mass, the distinctive feature of obesity, is associated with low-grade inflammation. White adipose tissue secretes a diverse range of adipokines, a number of which are inflammatory mediators (such as TNFα, IL-1β, IL-6, monocyte chemoattractant protein 1). The production of inflammatory adipokines is increased with obesity and these adipokines have been implicated in the development of insulin resistance and the metabolic syndrome. However, the basis for the link between increased adiposity and inflammation is unclear. It has been proposed previously that hypoxia may occur in areas within adipose tissue in obesity as a result of adipocyte hypertrophy compromising effective O2 supply from the vasculature, thereby instigating an inflammatory response through recruitment of the transcription factor, hypoxic inducible factor-1. Studies in animal models (mutant mice, diet-induced obesity) and cell-culture systems (mouse and human adipocytes) have provided strong support for a role for hypoxia in modulating the production of several inflammation-related adipokines, including increased IL-6, leptin and macrophage migratory inhibition factor production together with reduced adiponectin synthesis. Increased glucose transport into adipocytes is also observed with low O2 tension, largely as a result of the up-regulation of GLUT-1 expression, indicating changes in cellular glucose metabolism. Hypoxia also induces inflammatory responses in macrophages and inhibits the differentiation of preadipocytes (while inducing the expression of leptin). Collectively, there is strong evidence to suggest that cellular hypoxia may be a key factor in adipocyte physiology and the underlying cause of adipose tissue dysfunction contributing to the adverse metabolic milieu associated with obesity.

scholarly journals Dysfunctional adipose tissue and low-grade inflammation in the management of the metabolic syndrome: current practices and future advances

F1000Research ◽  
2016 ◽  
Vol 5 ◽  
pp. 2515 ◽  
Author(s):  
Marleen M. J. van Greevenbroek ◽  
Casper G. Schalkwijk ◽  
Coen D.A. Stehouwer
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Low Grade ◽  
Pharmacological Interventions ◽  
Obesity Epidemic ◽  
The Metabolic Syndrome ◽  
Adipose Tissue Dysfunction ◽  
Recent Developments ◽  
Low Grade Inflammation ◽  
The Complement System

The ongoing worldwide obesity epidemic makes the metabolic syndrome an increasingly important entity. In this review, we provide a short background on the metabolic syndrome, we discuss recent developments in the three main options that have been identified for intervention in the metabolic syndrome, i.e. lifestyle and surgical and pharmacological interventions, and we focus on different views in the literature and also include our own viewpoints on the metabolic syndrome. In addition, we discuss some emerging treatment targets for adipose tissue dysfunction and low-grade inflammation, i.e. activation of the inflammasome and the complement system, and consider some selected opportunities for intervention in these processes.

scholarly journals Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?

2008 ◽  
Vol 100 (2) ◽  
pp. 227-235 ◽  
Author(s):  
Paul Trayhurn ◽  
Bohan Wang ◽  
I. Stuart Wood
Keyword(s):  
Adipose Tissue ◽  
Inflammatory Response ◽  
Marker Gene ◽  
Hypoxia Inducible Factor ◽  
Subsequent Development ◽  
Obese Mouse ◽  
Human Adipocytes ◽  
Tissue Mass ◽  
Monocyte Chemoattractant Protein 1 ◽  
The Metabolic Syndrome

White adipose tissue is a key endocrine and secretory organ, releasing multiple adipokines, many of which are linked to inflammation and immunity. During the expansion of adipose tissue mass in obesity there is a major inflammatory response in the tissue with increased expression and release of inflammation-related adipokines, including IL-6, leptin, monocyte chemoattractant protein-1 and TNF-α, together with decreased adiponectin production. We proposed in 2004 (Trayhurn & Wood, Br J Nutr92, 347–355) that inflammation in adipose tissue in obesity is a response to hypoxia in enlarged adipocytes distant from the vasculature. Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models (ob/ob, KKAy, diet-induced) and molecular studies indicate that the level of the hypoxia-inducible transcription factor, hypoxia-inducible factor-1α, is increased, as is expression of the hypoxia-sensitive marker gene, GLUT1. Cell- culture studies on murine and human adipocytes show that hypoxia (induced by low O2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor and vascular endothelial growth factor. Hypoxia also stimulates the inflammatory response of macrophages and inhibits adipocyte differentiation from preadipocytes. GLUT1 gene expression, protein level and glucose transport by human adipocytes are markedly increased by hypoxia, indicating that low O2 tension stimulates glucose utilisation. It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases, particularly type 2 diabetes and the metabolic syndrome.

scholarly journals Obesity and lung inflammation

2010 ◽  
Vol 108 (3) ◽  
pp. 722-728 ◽  
Author(s):  
Peter Mancuso
Keyword(s):  
Adipose Tissue ◽  
Lung Disease ◽  
Inflammatory Responses ◽  
Acute Phase Proteins ◽  
Pulmonary Inflammation ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Tissue Mass ◽  
Proinflammatory Mediators ◽  
Increased Risk

The prevalence of obesity has increased dramatically worldwide, predisposing individuals to an increased risk of morbidity and mortality due to cardiovascular disease and type 2 diabetes. Less recognized is the fact that obesity may play a significant role in the pathogenesis of pulmonary diseases through mechanisms that may involve proinflammatory mediators produced in adipose tissue that contribute to a low-grade state of systemic inflammation. In animal models, inflammatory responses in the lung have been shown to influence the production of the adipocytokines, leptin and adiponectin, cytokines, acute phase proteins, and other mediators produced by adipose tissue that may participate in immune responses of the lung. An increased adipose tissue mass may also influence susceptibility to pulmonary infections, enhance pulmonary inflammation associated with environmental exposures, and exacerbate airway obstruction in preexisting lung disease. An increased understanding of the mechanisms by which obesity influences pulmonary inflammation may facilitate the development of novel therapeutic interventions for the treatment of lung disease.

scholarly journals Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Andrew A. Bremer ◽  
Ishwarlal Jialal
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Low Grade ◽  
The Metabolic Syndrome ◽  
Adipose Tissue Dysfunction ◽  
Increased Risk ◽  
Subcutaneous Adipose ◽  
Low Grade Inflammation

The metabolic syndrome (MetS) confers an increased risk for both type 2 diabetes mellitus (T2DM) and cardiovascular disease (CVD). Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT) in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin) and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin), as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

scholarly journals Chemotactic cytokines, obesity and type 2 diabetes:in vivoandin vitroevidence for a possible causal correlation?

2009 ◽  
Vol 68 (4) ◽  
pp. 378-384 ◽  
Author(s):  
Henrike Sell ◽  
Jürgen Eckel
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Low Grade ◽  
Obese Patients ◽  
Tissue Mass ◽  
Tissue Biology ◽  
Wide Range ◽  
Adipose Tissue Mass

A strong causal link between increased adipose tissue mass and insulin resistance in tissues such as liver and skeletal muscle exists in obesity-related disorders such as type 2 diabetes. Increased adipose tissue mass in obese patients and patients with diabetes is associated with altered secretion of adipokines, which also includes chemotactic proteins. Adipose tissue releases a wide range of chemotactic proteins including many chemokines and chemerin, which are interesting targets for adipose tissue biology and for biomedical research in obesity and obesity-related diseases. This class of adipokines may be directly linked to a chronic state of low-grade inflammation and macrophage infiltration in adipose tissue, a concept intensively studied in adipose tissue biology in recent years. The inflammatory state of adipose tissue in obese patients may be the most important factor linking increased adipose tissue mass to insulin resistance. Furthermore, chemoattractant adipokines may play an important role in this situation, as many of these proteins possess biological activity beyond the recruitment of immune cells including effects on adipogenesis and glucose homeostasis in insulin-sensitive tissues. The present review provides a summary of experimental evidence of the role of adipose tissue-derived chemotactic cytokines and their function in insulin resistancein vivoandin vitro.

scholarly journals NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 4184 ◽  
Author(s):  
Kelvin Ka-Lok Wu ◽  
Samson Wing-Ming Cheung ◽  
Kenneth King-Yip Cheng
Keyword(s):  
Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Immune Cell ◽  
Diabetic Patients ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Adipose Tissues ◽  
Adipose Tissue Dysfunction ◽  
Nlrp3 Inflammasome Activation

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade chronic inflammation and excessive immune cell infiltration, is a hallmark of obesity, as well as an important link to cardiometabolic diseases. Amongst the pro-inflammatory factors secreted by the dysfunctional adipose tissue, interleukin (IL)-1β, induced by the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, not only impairs peripheral insulin sensitivity, but it also interferes with the endocrine and immune functions of adipose tissue in a paracrine manner. Human studies indicated that NLRP3 activity in adipose tissues positively correlates with obesity and its metabolic complications, and treatment with the IL-1β antibody improves glycaemia control in type 2 diabetic patients. In mouse models, genetic or pharmacological inhibition of NLRP3 activation pathways or IL-1β prevents adipose tissue dysfunction, including inflammation, fibrosis, defective lipid handling and adipogenesis, which in turn alleviates obesity and its related metabolic disorders. In this review, we summarize both the negative and positive regulators of NLRP3 inflammasome activation, and its pathophysiological consequences on immunometabolism. We also discuss the potential therapeutic approaches to targeting adipose tissue inflammasome for the treatment of obesity and its related metabolic disorders.

scholarly journals Recent Advances in Adipose Tissue Dysfunction and Its Role in the Pathogenesis of Non-Alcoholic Fatty Liver Disease

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3300
Author(s):  
Xiaoxiao Wang ◽  
Huiying Rao ◽  
Feng Liu ◽  
Lai Wei ◽  
Honggui Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Current Knowledge ◽  
Low Grade ◽  
Alcoholic Fatty Liver ◽  
Nonalcoholic Fatty Liver ◽  
Adipose Tissue Dysfunction ◽  
Adipose Dysfunction

Obesity is a serious ongoing health problem that significantly increases the incidence of nonalcoholic fatty liver disease (NAFLD). During obesity, adipose tissue dysfunction is obvious and characterized by increased fat deposition (adiposity) and chronic low-grade inflammation. The latter has been implicated to critically promote the development and progression of NAFLD, whose advanced form non-alcoholic steatohepatitis (NASH) is considered one of the most common causes of terminal liver diseases. This review summarizes the current knowledge on obesity-related adipose dysfunction and its roles in the pathogenesis of hepatic steatosis and inflammation, as well as liver fibrosis. A better understanding of the crosstalk between adipose tissue and liver under obesity is essential for the development of new and improved preventive and/or therapeutic approaches for managing NAFLD.

scholarly journals Osteopontin – a multifunctional protein and its impact on an insulin resistance development

2014 ◽  
Vol 83 (2) ◽  
pp. 173-176
Author(s):  
Katarzyna Musialik ◽  
Damian Skrypnik ◽  
Paweł Bogdański ◽  
Monika Szulińska
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Process ◽  
Blood Stream ◽  
Interleukin 12 ◽  
Low Grade ◽  
Tissue Mass ◽  
Multifunctional Protein ◽  
Artery Disease ◽  
The Many

Osteopontin (OPN) is one of the many physiological elements creating human musculoskeletal system. It is suspected that this protein is one of the most important mediators responsible for osseous tissue mass resorption, regulated by parthormon. The origin of its name comes from one of its physiological action – rebuilding of the bone mass structure (osteo – bone, pontin – bridge). Osteopontin fulfils many different actions being secreted by many different types of cells, including macrophages, lymphocytes, epithelial cells, vascular smooth muscle cells, and osteoblasts. OPN plays an important part in inflammatory process. It provokes macrophages and dendritic cells to movement into the destination where inflammatory process takes place. It also stimulates macrophages to interleukin 12 (IL12) and interferon ? (IFN ?) secretion. Increased OPN concentration in blood stream might be regarded as a novel, independent indicator of coronary artery disease. Osteopontin plays an important role in macrophage infiltration of the adipose tissue and at the same time contributes to insulin resistance. Obesity induces chronic, low-grade tissue inflammation. Positive correlation was observed between body mass index (BMI) and number of macrophages accumulated in the fat tissue. Once aroused monocytes infiltrate the adipose tissue, which leads to persisting chronic inflammation. At the same time the excreted by them cytokines may be connected with the mechanisms of obesity-induced insulin resistance.

scholarly journals Adipose Tissue Remodeling as Homeostatic Inflammation

2011 ◽  
Vol 2011 ◽  
pp. 1-8 ◽  
Author(s):  
Michiko Itoh ◽  
Takayoshi Suganami ◽  
Rumi Hachiya ◽  
Yoshihiro Ogawa
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Saturated Fatty Acids ◽  
Tissue Remodeling ◽  
Low Grade ◽  
Adipose Tissue Inflammation ◽  
Tissue Inflammation ◽  
Adipose Tissue Remodeling ◽  
Novel Therapeutic Strategies

Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

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