Obesityinduced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple. Cellular and molecular players in adipose tissue inflammation in the development of obesityinduced insulin resistance. Metabolic changes in these cells also contributed to the. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a. It seems clear that tnfa is a powerful autocrine and paracrine regulator of adipose tissue.
Accumulating evidence indicates that cardiovascular disease is the collateral damage of obesitydriven adipose tissue dysfunction that promotes a chronic inflammatory state within the organism. Here, we demonstrate that the ho1 inducer, hemin, protects against obesityinduced. By contrast, obesityinduced inflammation is thought to mainly occur in the tissueinfiltrating immune cells. The role of adipose tissue and adipokines in obesity. This leads the body to a proinflammatory pattern, which may affect the proper functioning of many tissues. Obesity is causally linked with the development of cardiovascular disorders. Obesityinduced inflammatory changes in adipose tissue ncbi. Obesity is associated with inflammation in adipose tissue, namely an infiltration and expansion of macrophages, which produce inflammatory cytokines that interfere with insulin signaling, and a loss of protective cells that promote adipose homeostasis.
Obesity is associated with a chronic lowgrade inflammation of adipose tissue characterized by. Proinflammatory, m1 phenotype macrophages and the cjun nh2 terminal kinases jnk are central players in this process. White adipose tissue is the primary site of energy storage and the release of hormones and cytokines that modulate wholebody metabolism and insulin resistance 27,28. Obesity and the role of adipose tissue in inflammation and. Changes in energy stores induced by food deprivation, overfeeding, or excess. Noncanonical wnt signaling promotes obesityinduced. Adipose tissue inflammation in the pathogenesis of type 2. During the expansion of adipose tissue, a number of functions such as activation and release of cytokines and hormones may be affected. Hilpda uncouples lipid droplet accumulation in adipose. Obesity stimulates chronic inflammation in adipose tissue, which is associated with insulin resistance, although the underlying mechanism remains largely unknown. Ask1 inhibits browning of white adipose tissue in obesity.
Obesityinduced changes in adipose tissue microenvironment. Accumulating evidence has demonstrated that obesity is the most important and common cause of insulin resistance 3, 4. Obesityinduced adipose tissue inflammation is associated with systemic insulin resistance and hyperinsulinaemia in obese rodents and humans. Obesity, adipose tissue, inflammation and update on.
Here we showed that obesityrelated adipocyte degeneration causes release of cellfree dna cfdna, which promotes macrophage accumulation in adipose tissue via tolllike receptor 9 tlr9, originally known as a. Obese adipose tissue is characterized by inflammation journal of. But whether jnk expression is specifically required inside macrophages is unclear. The development of these metabolic diseases is associated with changes in both the number and phenotype of adipose tissue macrophages atms. Metabolic regulation of adipose tissue macrophage function. Adipose macrophages with the antiinflammatory m2 phenotype protect against obesityinduced inflammation and insulin resistance. The role of adipose tissue immune cells in obesity and lowgrade. Immune cells are of particular relevance in this regard. Role of nkg2d in obesityinduced adipose tissue inflammation and insulin resistance junjae chung1, mary a. On the other hand, activation of inflammatory pathways in adipocytes impairs. Adipose tissue dysfunction plays a pivotal role in the development of insulin resistance in obese individuals. Obesityinduced macrophage accumulation in adipose tissue 40 obesityinduced inflammation and insulin resistance. Obesity as an inflammatory agent can cause cellular changes in human milk due to the actions of the adipokines leptin and adiponectin.
Obesityinduced changes in their number and activity result. However, our current understanding of obesityassociated insulin resistance relies on studies of artificial metabolic extremes. Heme oxygenase1 ho1, which elicits antioxidant and antiinflammatory activity, modulates macrophage phenotypes and thus is implicated in various inflammatory diseases. Lipoxinmediated protection was adiponectin independent, but correlated with restored. Obesityinduced changes in adipose tissue microenvironment and their impact on cardiovascular disease. Obesity is accompanied by a chronic inflammation of adipose tissue, and this. During obesity, adipose tissue changes the number and size of. 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. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. Salicylates and thiazolidinediones tzds both have antiinflammatory and antihyperglycemic properties. Differential role of adipose tissues in obesity and. Two manuscripts in this issue of the jci see the related articles beginning on pages 1796.
Lipoxins mediated protection by decreasing adipose inflammation and promoting a macrophage m1tom2 switch. Induction of heme oxygenase1 with hemin reduces obesity. Lipoxina4 and a synthetic lipoxin analog protected against obesityinduced kidney and liver disease. Aims to determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. Eicosapentaenoic acid shows antiinflammatory effect via. 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. Several studies show that obesity changes the number and functions of the various types of immune cells in the at svc fraction. Trem2 regulates obesityinduced insulin resistance via. Overweight and obesity account for a major proportion of type 2 diabetes t2d cases. Adipose tissue is not only a reservoir for energy, but also an immune organ. Obesity leads to a state of chronic, lowgrade inflammation that features the accumulation of lipidladen macrophages in adipose tissue. Adiponectin resistance and proinflammatory changes in the. 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.
Lipoxin a4 attenuates obesityinduced adipose inflammation. Development of obesityinduced inflammation and insulin. It is increasingly accepted that chronic inflammation participates in obesityinduced insulin resistance and type 2 diabetes t2d. Obesityinduced proinflammatory cytokines and lps polarize kc towards m pro that in turn. The adipose tissue pool in mammals is composed of at least two functionally distinct types of fat. In fact, insulin has been assigned with both anti and proinflammatory properties. Cellular and molecular players in adipose tissue inflammation in the. Weight gain in obesity generates excess of fat, usually visceral fat, and activates the inflammatory response in the adipocytes and then in other tissues such as liver. Although the mechanisms involved in this association are poorly understood, it is well appreciated that obesityinduced changes in adipose tissue could affect whole body metabolism and inflammatory responses through secreted mediators. Dietary intake of bioactive ingredients impacts liver and. Obesity induced by high fat hf diet is associated with inflammation which contributes to development of insulin resistance.
Exercise, inflammation, and innate immunity pdf free. However, little is known about the relationship of these receptors in dietinduced obesity dio. Obesity is highly prevalent all over the world, due to changes in our lifestyle and diet 1, 2. Obesity and diabetes are associated with chronic activation of inflammatory pathways that are important mechanistic links between insulin resistance ir, type 2 diabetes t2d, and cardiovascular disease pathogenesis. 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. Chronic, lowgrade inflammation is a major hallmark of the obese adipose tissue, and it. Obesityinduced inflammatory changes in adipose tissue journal of.
Noncanonical wnt signaling promotes obesityinduced adipose tissue inflammation and metabolic dysfunction independent of adipose tissue expansion. Our interest in this protein originated over 12 years ago when, by comparing the expression profile of white adipose tissue wat in lean vs obese mice, hp mrna emerged as dramatically upregulated in the latter. Obesityinduced inflammatory changes in adipose tissue kathryn e. Regulation of dietinduced adipose tissue and systemic. 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. We have shown that tlr4 deficient c57bl10scn mice were protected against dio, specifically when mice were. Adipose tissueresident immune cells in obesity and. Pdf obesityinduced inflammatory changes in adipose. 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 fructoseinduced khkdependent proinflammatory changes in the adipose tissue figs. It also activates an inflammatory process in metabolically active sites, such as white adipose tissue, liver, and immune cells.
Adipose tissue, obesityinduced inflammation, and insulin resistance there are two distinct forms of at, brown adipose tissue bat and white adipose tissue wat. At inflammation was proposed as a central mechanism connecting obesity with its metabolic and vascular complications. However, no genetic evidence supports a role for endogenous wnt proteins in adipose tissue dysfunction, and the role of noncanonical wnt signaling. The importance of the immune system in wholebody energy balance provides a rationale for the links between cytokines and adipose tissue. Increasing evidence links intestinal bacteria to development of dietinduced obesity dio. In the context of obesity, the development of insulin resistance is now recognised to be initiated by inflammation of the adipose tissue. Jci obesityinduced inflammatory changes in adipose tissue. Obesityinduced dna released from adipocytes stimulates. In mice containing a macrophagespecific deletion in both jnk1 and jnk2, han et al. Obesityinduced adipose tissue inflammation as a strong promotional factor for pancreatic ductal adenocarcinoma.
Molecular and cellular mechanisms of cardiovascular disorders in diabetes. Grn progranulin chemoattractant protein involved in adipose tissue inflammation and neurodegenerative diseases. Shaw1,3 1department of pathology and immunology, washington university school of medicine, st. Obesity is an energyrich condition associated with overnutrition, which impairs systemic metabolic homeostasis and elicits stress. We found that a highfat diet increased tlr9 expression in vat and that the expression of. The ubiquitin ligase siah2 regulates obesityinduced. Macrophage function in obesityinduced inflammation and. Background nowadays, the number of obese people in the world has reached alarming proportions. Louis, missouri, united states of america, 2department of. Although ubiquitin ligases regulate inflammatory processes, the role of these enzymes in metabolically driven adipose tissue inflammation is relatively unexplored.
Cell culture studies and gainoffunction mouse models suggest that canonical wnt proteins modulate adipose tissue expansion. The roles of adipokines, proinflammatory cytokines, and. Multifaceted haptoglobin in the context of adipose tissue. Excessive adipocyte hypertrophy initiates changes in the inflammatory characteristics of the adipocyte that include greater nf. At the cellular level, obesityinduced insulin resistance is caused by the impairment of the insulin signaling pathway in insulinresponsive cells i. Obesity is associated with a state of chronic, lowgrade inflammation. The infrapatellar fat pad ifp is an adipose tissue depot in the knee joint. Heart failure considerations of antihyperglycemic medications for type 2 diabetes. Increasing evidence suggests that cfdna serves as an endogenous ligand for tlr9, contributing to the pathogenesis of several inflammatory diseases 4, 69, 25, although the role of tlr9 in adipose tissue inflammation remains unknown.
Innate immunity and inflammation interleukin17 and innate immunity in infections and chronic inflammation innate immunity. Inflammation is thought to be an important driver of dietinduced obesity and insulin resistance. Information about the openaccess article obesityinduced diet leads to weight gain, systemic metabolic alterations, adipose tissue inflammation, hepatic steatosis, and oxidative stress in gerbils meriones unguiculatus in doaj. Multiple lines of evidence suggest that insulin itself directly affects inflammatory processes. Given the complexity of the immune cell changes and inflammatory responses in the at during obesity, with the multitude of inflammatory mediators, targeting single or even few. This group proposed that various obesityinduced mediators e. Materials and methods male c57bl6 mice were placed on a control or highfat diet hfd and were maintained on such diets for the duration of the study.
The relationship between obesity and inflammation was emerging as a hot and novel topic in those years, prompted by the observation that obese subjects. Here, we determined the role of macrophage lipiddroplet accumulation in the development of obesityinduced adiposetissue inflammation, using mice with myeloidspecific deficiency of the lipidinducible hilpda protein. Niacin increases adiponectin and decreases adipose tissue. The present study compared the effects of these drugs on obesityinduced inflammation in adipose tissue at and at macrophages atms, as well as the. Jnk expression by macrophages promotes obesityinduced. Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Obesityinduced diet leads to weight gain, systemic. Most prior studies have focused on adipose tissue as the source of obesityassociated inflammation. Chronic, lowgrade adipose tissue inflammation associated with adipocyte hypertrophy is an important link in the relationship between obesity and insulin resistance. Obesityinduced inflammatory changes in adipose tissue core. Mechanisms of obesityinduced inflammation and insulin. Two manuscripts in this issue of the jci see the related articles. The purpose of this study was to explore the roles of adipokines, proinflammatory cytokines. The aims of the present study were to determine the antiinflammatory effects of epa via gpr120 in cultured adipocytes, and to clarify the effects of epa supplementation on highfathighsucrose hfhs dietinduced inflammatory changes in adipose tissue.
Adapting to obesity with adipose tissue inflammation. Abstractexcerpt full text pdf adipose tissue at lies at the crossroad of nutrition, metabolism, and immunity. These antiinflammatory cells include regulatory cd4 t cells tregs, th2 cd4 t cells, and. Obesityinduced inflammatory changes in adipose tissue. Differential role of adipose tissues in obesity and related.
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