The protein mincle can sense pathogens and molecules associated with cell death. Adipose tissue inflammation and liver pathology in human. Understanding the molecular mechanism underlying adipose tissue remodeling may lead to the identification of novel therapeutic strategies to prevent or treat obesity induced adipose tissue inflammation. Obesity induced inflammatory changes in adipose tissue. White wat and brown bat adipose tissue communicate with skeletal muscle and heart through the secretion of adipokines adiponectin, leptin, omenti. Download citation visceral adipose tissue activated macrophage content and inflammatory adipokine secretion is higher in preeclampsia than in healthy pregnancy obesity increases preeclampsia. Nov 12, 2012 to examine the relationship between obesity induced er stress and chronic inflammation, we determined the mrna expression levels of inflammatory genes in adipose tissue of mice fed a highfat diet. The role of inflammation in the development of obesityinduced insulin resistance was first suggested by the early studies on tnf.
Here we showed that obesity related adipocyte degeneration causes release of cellfree dna cfdna, which promotes macrophage accumulation in adipose tissue via tolllike receptor 9 tlr9, originally known as a sensor of exogenous. Development of obesityinduced inflammation and insulin. Cumulating evidence suggest a model in which diet induced obesity leads to a robust inflammatory response in visceral peripancreatic or intrapancreatic adipose tissue, which may in turn promote inflammation and neoplastic progression in the neighboring pancreas, via soluble factors secreted from adipocytes andor adipose infiltrating. Based on the widely accepted concept that lowgrade inflammation in the adipose tissue in obesity is a major cause of insulin resistance and cardiovascular risk 27,40,41, we believe that fructose induced khkdependent proinflammatory changes in the adipose tissue figs. Particular focus is placed on how the gastrointestinal tract that is connected to visceral adipose tissue via the lymphatic system may play a role in differential metabolic outcomes of distinct adipose tissue distributions. Two manuscripts in this issue of the jci see the related articles beginning on pages 1796. Atms are a prominent source of proinflammatory cytokines, such as tnf. Jci obesityinduced inflammatory changes in adipose tissue. Nk cells link obesityinduced adipose stress to inflammation. Two manuscripts in this issue of the jci see the related articles.
Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue david a. An important early event in vat inflammation is the activation of macrophages in adipose tissue. Changes in adipocyte and fat pad size lead to physical changes in the surrounding area and modifications of the paracrine function of the adipocyte. In obesity, proinflammatory responses are rapidly elevated in visceral adipose tissue, whereas inflammatory responses in subcutaneous adipose tissues are relatively downregulated. Obesity, bioactive lipids, and adipose tissue inflammation in insulin resistance author. Obesity, diabetes, and cardiovascular diseases compendium.
Obesityinduced inflammatory changes in adipose tissue pdf. Obesity induced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Bat is typically associated with thermogenesis, although initially thought to disappear soon after birth in humans, evidence now suggests that bat is present in adult humans in the. Highlightsvisceral adipose tissue and the gastrointestinal tract mutually influence immune cells of the visceral lymph node. Increased inflammatory properties of adipose tissue. In the visceral lymph node adipose cytokine effluent causes expansion, survival and retention of pro inflammatory. Earlier transcriptional profiling experiments performed in adipose tissue from lean and obese animal models, or following treatment of obese animals with members of the thiazolidinedione class of antidiabetic agents, have pointed to striking regulation of a large repertoire of inflammatory genes in adipose tissue. Obesity is a major risk factor for the development of insulin resistance and type 2 diabetes.
Targeting inflammationinduced obesity and metabolic. Despite several studies have focused on microrna expression profiles and functions in different metabolic tissues, little is known about their response to nutritional interventions in white adipose tissue during obesity stages, and whether they differ in this. These studies prompt consideration of new models to include a major role for macrophages in the molecular changes that occur in adipose tissue. Two manuscripts in this issue of the jci see the related articles beginning on pages 1796 and 1821 now report that obese adipose tissue is characterized by macrophage infiltration and that these. Obesityassociated inflammation and loss of muscle function play critical roles in the development of osteoarthritis oa. The role of adipose tissue immune cells in obesity and low. In vivo imaging of obesityinduced inflammation in adipose. Adipose tissue hypoxia, inflammation, and fibrosis in. Obesity is associated with a state of chronic, lowgrade inflammation. Distinct macrophage populations direct inflammatory versus. Heart failure considerations of antihyperglycemic medications for type 2 diabetes. We hypothesized that atms recruited to adipose tissue during a highfat diet have unique inflammatory properties compared with resident tissue atms. Sep, 2016 therefore, suppression of inflammatory responses in the interaction of adipocytes and macrophages within adipose tissue is considered to have beneficial effects in ameliorating obesity.
Expression profiling and analysis of some mirnas in. Cellular and molecular players in adipose tissue inflammation in the development of obesityinduced insulin resistance. Frontiers mechanisms of obesityinduced inflammation and. Activation and regulation of the pattern recognition. Obesityassociated inflammation stems from a combination of cellintrinsic changes of individual immune cell subsets and the dynamic crosstalk amongst a broad array of immune cells.
Inhibiting glycogen synthase kinase 3 reverses obesity. Obesityinduced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Adipose tissue inflammation in the pathogenesis of type 2. During obesity, the adipose tissue is inflamed and secretes proinflammatory adipokines leptin, resistin, visfatin, lipocalin2, chemerin and cytokines tnf. Obesityinduced inflammatory changes in adipose tissue kathryn e. Obesity is characterized by the development of a lowgrade chronic inflammatory state in different metabolic tissues including adipose tissue and liver. The roles of at immune cells in the development of obesity induced inflammation. Obesityinduced inflammation and insulin resistance. Mechanisms of obesityinduced inflammation and insulin. Both celltypes express the lxa 4 receptor alxfpr2 and are susceptible to the anti inflammatory actions of lxa 4 borgeson et al. Hotamisligil department of genetics and complex diseases, harvard school of public health, boston, massachusetts, usa obesity is associated with a state of chronic, lowgrade inflammation.
First, tlr4 expression is increased in adipose tissue inflammatory macrophages in obesity 46,47. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. Two manuscripts in this issue of the jci see the related articles beginning on pages 1796 and 1821 now report that obese adipose tissue is characterized by macrophage infiltration and that these macrophages are an important source of inflammation in this tissue. In vivo imaging of obesityinduced inflammation in adipose tissue. Micrornas are emerging as new mediators in the regulation of adipocyte physiology and have been approved to play a role in obesity. Adipose tissue at histopathology and inflammatory gene expression as well as hepatic lipid content were analyzed after sacrifice. Evidence has accumulated indicating that obesity is associated with a state of chronic, lowgrade inflammation.
Aug 11, 2017 adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Cd11b regulates obesityinduced insulin resistance via. Adipose tissue depot differences in adipokines and effects. Noncanonical wnt signaling promotes obesityinduced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion. Distribution of adipose tissue is important in the metabolic complications of obesity. Ledoux s, queguiner i, msika s, calderari s, rufat p, gasc jm, corvol p, larger e. Cd11b regulates obesityinduced insulin resistance via limiting alternative activation and proliferation of adipose tissue macrophages chunxing zheng a, qian yang, chunliang xu a, peishun shou, jianchang cao, menghui jiang, qing chen, gang caoa, yanyan hana, fengying lia, wei caoa, liying zhangb, li zhangc, yufang shia,b,d,1, and ying wanga,1 akey laboratory of stem cell biology. As a result, obesityinduced inflammation had placed the adipose tissue at the center of inflammation related pathophysiology. Visceral adipose tissue activated macrophage content and. Abstractcontext a substantial number of obese individuals are relatively insulin sensitive and the etiology for this variation remains unknown. When storage capacity of adipose tissue exceeds its limit for fat deposition, spillage of ffa and adipokines alters inflammatory states in various tissues causing etiology of type 2 diabetes and vascular disease figure. Adipose tissue, obesityinduced inflammation, and insulin resistance there are two distinct forms of at, brown adipose tissue bat and white adipose tissue wat. Tissue immune cells fuel obesityassociated inflammation.
Early studies by hotamisiligil and subsequent studies identified adipose tissue as an important source of obesity. Second, tlr4 knockout ko mice or mice with a lossoffunction mutation in the tlr4 gene are protected from obesity induced insulin resistance 46,48. Thus, these studies also suggest that ginger has potential in preventing obesity and obesitylinked metabolic effects. Lipoxin a4 attenuates obesityinduced adipose inflammation. We have shown that tlr4 deficient c57bl10scn mice were protected against dio, specifically when mice were. Adiponectin resistance and proinflammatory changes in the.
Adipose tissue, when carried around in excessive amounts, predisposes to a large number of diseases. Pdf obesityinduced adipose tissue inflammation as a. Role of nkg2d in obesityinduced adipose tissue inflammation. The innate immune receptors, tolllike receptor2 tlr2 and tolllike receptor4 tlr4, are implicated in the development of inflammation and insulin resistance in various cell populations. A key feature in the reversible nature of obesityinduced changes in at is the attenuation of inflammatory and immune pathways both in. Dysfunctional at lipid metabolism leads to increased circulating free fatty acids, initiating inflammatory. Abdominal adipose tissue, which is strategically located to the liver, is. Obesity, bioactive lipids, and adipose tissue inflammation. Overweight and obesity account for a major proportion of type 2 diabetes t2d cases. Obesityinduced adipose tissue inflammation as a strong promotional factor for pancreatic ductal adenocarcinoma article pdf available july 2019 with 62 reads how we measure reads. Obesity is associated with lowgrade inflammation in adipose tissue, which contributes to the development of obesityrelated diseases such as insulin resistance, hypertension and arteriosclerosis. Obesityinduced endoplasmic reticulum stress causes. Role of nkg2d in obesityinduced adipose tissue inflammation and insulin resistance junjae chung1, mary a.
Here, we show that adipocyte plateletderived growth factor receptor. Recent studies have pointed to chronic inflammation in insulin target tissues, such as muscle, liver, and adipose tissue, as one of the causal links between obesity and insulin resistance. The secretion of chemoattractants such as mcp1 and mif and of cytokines il6, tnf. Jci citations to obesityinduced inflammatory changes in. Obesityinduced inflammatory changes in adipose tissue. Follistatin fst, a protein that binds myostatin and activin, may have the potential to enhance muscle formation while. Adipose tissue inflammation and ectopic lipid accumulation. Sphingolipid metabolism and obesityinduced inflammation. Although much of the focus of immune cell contributions to metabolic disease has focused on adipose tissue associated cells, these potent sources of inflammation inhabit other metabolic regulatory. It has been demonstrated that obesity is associated with the adipocyte dysfunction, macrophage infiltration, and lowgrade inflammation, which probably contributes to the induction of insulin resistance. Adipose tissue is heterogeneous and comprised of numerous celltypes, where adipocytes and m. Chronic, lowgrade inflammation is a major hallmark of the obese adipose tissue, and it.
Obese adipose tissue is characterized by inflammation 1 and progressive infiltration by macrophages as obesity develops 10, 11. Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Obesityinduced white adipose tissue wat fibrosis is believed to accelerate wat dysfunction. Obesityinduced insulin resistance and hepatic steatosis.
Although recent studies show that adipose tissue macrophages atms participate in the inflammatory changes in obesity and contribute to insulin resistance, the properties of these cells are not well understood. Obesity and associated chronic inflammation initiate a state of insulin resistance ir. Obesityinduced changes in adipose tissue microenvironment. Obesityinduced inflammatory changes in adipose tissue ncbi. These studies prompt consideration of new models to include. The switch from a lfd to a hfd lowered the respiratory exchange ratio and increased plasma cholesterol and hepatic lipid content. Immune cells are of particular relevance in this regard. This inflammation develops in response to an excess of nutrient flux and is now recognized as an important link between obesity and insulin resistance.
The exact mechanism by which adipose tissue induces insulin resistance is still unclear. Obesityinduced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple. As obesityinduced inflammation promotes metabolic dysfunction followed by impaired insulin signaling 32, we conducted immunoblotting to assess the insulin signaling status in adipose tissue. Obesityinduced insulin resistance is tightly associated with increased inflammation in obese white adipose tissue wat as indicated by increased infiltration of multiple types of proinflammatory immune cells into wat. However, little is known about the relationship of these receptors in dietinduced obesity dio.
To clarify the cellular targets affected by lxs in this model, we designed a. Obesityinduced endoplasmic reticulum stress causes chronic. Lipoxina4 and a synthetic lipoxin analog protected against obesityinduced kidney and liver disease. Hotamisligil published december 15, 2003 citation information. Adipose tissue macrophages are largely responsible for tnf. Gene therapy for follistatin mitigates systemic metabolic. Obesityinduced inflammatory changes in adipose tissue core. Under lean conditions, adipose tissueresident macrophages have an antiinflammatory m2like phenotype. Zingerone, another component of ginger, was found to suppress the inflammatory responses of adipose tissue in obesity by suppressing the inflammatory action of macrophages and release of mcp1 from adipocytes. Obesity and osteoarthritis, more than just wear and tear. Nonetheless, among the adipose tissue components other than immune cells, the modulators of fat depotselective inflammatory. Obesityinduced endoplasmic reticulum stress causes chronic inflammation in adipose tissue article pdf available in scientific reports 2article 799.
However, how adipose tissue stress is translated into a signal that activates the immune system is largely unknown. B have been implicated in obesityinduced insulin resistance. Adipose tissue, obesityinduced inflammation, and insulin resistance. At inflammation was proposed as a central mechanism connecting obesity with its metabolic and vas. Molecular and cellular mechanisms of cardiovascular disorders in diabetes. Effects of anthocyanin and flavanol compounds on lipid. A model emerged in which adipocytes were the primary source and the local target of these inflammatory factors. Adipose tissue remodeling as homeostatic inflammation. Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Lipoxins mediated protection by decreasing adipose inflammation and promoting a macrophage m1tom2 switch. Lipoxinmediated protection was adiponectin independent, but correlated with restored adipose. However, the cellular origin of wat fibrosis remains unclear. Cellular and molecular players in adipose tissue inflammation.
In contrast, adipocyte hypertrophy typically leads to lipidladen, dysfunctional adipocytes that undergo cell death and contribute to adipose tissue inflammation, dysfunction, and associated pathologies. The role of adipose tissue immune cells in obesity and lowgrade. Obesity is characterized by chronic lowgrade inflammation and macrophage accumulation in white adipose tissue wat. These cells regulate metabolism by producing proinflammatory cytokines, such as tnf, that compromise glucose homeo.
Louis, missouri, united states of america, 2department of histology and. Here the authors show that mincle expressed in macrophages is a mediator of obesityinduced fibrosis and. Shaw1,3 1department of pathology and immunology, washington university school of medicine, st. Obesityinduced adipose tissue inflammation as a strong. Macrophageinducible ctype lectin underlies obesity. Dysregulation of endocrine function and inflammation of adipose tissue at induce lowgrade systemic inflammation and insulin resistance in obese patients, which are implicated in the pathophysiology of type 2 diabetes mellitus t2dm. Pdf obesityinduced endoplasmic reticulum stress causes. Changes in adipose tissue immune status affect its cytokine content and consequently adipocyte metabolism and insulin sensitivity.
Obesityinduced dna released from adipocytes stimulates. Adipokines may act as autogenic regulators of body fat depots, modulating gastrointestinal activities, metabolic changes, and central nervous mechanisms, which may play a. Obesityinduced inflammatory changes in adipose tissue jci. Adipose tissue is a highly insulinresponsive organ that largely contributes to both glucose and lipid metabolism. Adipose tissue is considered an endocrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. Adipose tissue at lies at the crossroad of nutrition, metabolism, and immunity. Hill a,b,1, heewoong lim a,c,1, yong hoon kim a,d, wesley y. Mice treated with vehicle showed a significant increase in levels of insulin receptor substrate irs1 phosphorylated at ser307 irs1ps figure 5d, e. Adapting to obesity with adipose tissue inflammation nature. Altmetric implication of inflammatory signaling pathways. Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. The roles of adipokines, proinflammatory cytokines, and. Dec 15, 2003 obese adipose tissue is characterized by inflammation and progressive infiltration by macrophages as obesity develops 10, 11.
Obesity is associated with inflammation in adipose tissue, namely an infiltration and expansion of macrophages, which produce inflammatory cytokines that interfere with. Pdf obesity is associated with a state of chronic, lowgrade inflammation. The recently discovered role of adipose tissue as not only an inert storage depot but also a source of adipokines such as leptin, adiponectin, resistin, tnf. Adapting to obesity with adipose tissue inflammation. Iwona kojta, marta chacinska and agnieszka blachniozabielska subject. Pdf obesityinduced inflammatory changes in adipose. Epidemiological data show that the prevalence of obesity has significantly increased over the past 20 years and continues to do so at an alarming rate.
1523 721 1531 1501 516 219 1352 145 757 947 205 1204 212 1227 456 983 963 870 1392 1211 1351 1375 1236 142 170 1294 1318 1081 1307 273 425 953 1161 370 301 78 807 1162 1323