It is increasingly accepted that chronic inflammation is a feature of obesity. Tlr3 is present in human adipocytes, but its signalling is. Obesityinduced insulin resistance is a major risk factor for type 2 diabetes, hyperlipidemia, cardiovascular disease, and some types of cancer 1 3. B activation by combining implantation of 3t3l1 pre. Hotamisligil published december 15, 2003 citation information. Blocking il6 transsignaling prevents highfat dietinduced. Dec 20, 20 chronic nutrient excess leads to visceral adipose tissue vat expansion and dysfunction in an active process that involves the adipocytes, their supporting matrix, and immune cell infiltrates. Adipocytes become hypertrophic and immune cells, such as macrophages 3,4, t and bcells. Isolated adipocytes prepared from these tissues also released il6 omental sc, but this accounted for only 10%. Modulation of obesityinduced inflammation by dietary fats. 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. Jci obesityinduced inflammatory changes in adipose tissue. Obesity, adipose tissue, inflammation and update on obesity.
Our data are consistent with thisrapa treatment in het3 mice of both sexes strongly polarizes atms toward m1, and this was accompanied by increased proinflammatory expression of mcp1, tnf. Two manuscripts in this issue of the jci see the related articles beginning on pages 1796. In vivo imaging of obesityinduced inflammation in adipose. Development of obesity leads to morphological and functional changes in adipose tissue. Dec 15, 2003 obese adipose tissue is characterized by inflammation and progressive infiltration by macrophages as obesity develops 10, 11. The seminal finding that the expression of a proinflammatory cytokine, tumor necrosis factor. The role of adipose tissue and adipokines in obesity. A pioneering epidemic study has revealed a strong association between obesity and the risk of colitis. Deep sequencing of the transcriptome reveals inflammatory. Omental adipose tissue released 23 times more il6 than did sc adipose tissue. Role of nkg2d in obesityinduced adipose tissue inflammation and insulin resistance junjae chung1, mary a. Targeting inflammationinduced obesity and metabolic.
It also activates an inflammatory process in metabolically active sites, such as white adipose tissue, liver, and immune cells. Obesity is a strong risk factor for resistance to insulinmediated glucose disposal, a precursor of type 2 diabetes and other disorders. In this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a highcalorie diet and supplemented with. Depending on their phenotype, macrophages can be designated either as pro. This group proposed that various obesityinduced mediators e.
In vivo imaging of obesityinduced inflammation in adipose tissue. Obesity and the role of adipose tissue in inflammation and metabolism andrew s greenberg. Furthermore, the adipocytes in individuals who are obese. Tlr3 is present in human adipocytes, but its signalling. Lipoxinmediated protection was adiponectin independent, but correlated with restored adipose.
Adipose tissue, inflammation and cardiovascular disease scielo. Innate immunity plays a pivotal role in obesityinduced lowgrade inflammation originating from adipose tissue. Furthermore, the adipocytes in individuals who are obese are larger than those in people of average weight, and produce a lower level of adiponectin, but higher levels of pro inflammatory. These cells may contribute to lowgrade inflammation and to its metabolic. However, not all obese individuals are insulin resistant. Jun 15, 2011 obesity is associated with lowgrade chronic inflammation. In the context of obesity, the development of insulin resistance is now recognised to be initiated by inflammation of the adipose tissue. Obesity induced inflammatory changes in adipose tissue. Obesity, adipose tissue, inflammation and update on. Aug 11, 2017 adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. The accumulation in adipose tissue of macrophages in an inflammatory state is a hallmark of obesityinduced insulin resistance. Obesityinduced inflammatory changes in adipose tissue kathryn e. Obesityinduced inflammatory changes in adipose tissue. Adipose tissue is not only a reservoir for energy, but also an immune organ.
Pdf obesity is associated with a state of chronic, lowgrade inflammation. 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. Changes in adipocyte and fat pad size lead to physical changes in the surrounding area and modifications of the paracrine function of the adipocyte. Two manuscripts in this issue of the jci see the related articles.
The recruitment of immune cells into adipose tissue is a hallmark of obesity and a key event contributing to the development of adipose tissue inflammation and insulin resistance. In addition, the adipose tissue macrophages in diet induced obesity tend to have a pro inflammatory m1 phenotype, involving il6, il12, and tnf 51. A novel antiinflammatory role for spleenderived interleukin. Obesity induced adipose tissue inflammation and insulin resistance, role of the adipocyte in development of type 2 diabetes, coleen croniger, intechopen, doi. This obesity induced inflammatory state involves a phenotypic switch in adipose tissue macrophage from m2 to m1 state 23, 24. Systemic inflammatory changes lowgrade systemic inflammatory state production and secretion of adipocytokines involved in oa development obesity comorbidities hypertension, impaired glucose and lipid metabolism alter joint tissue homeostasis 1 1. Jci insulin resistance causes inflammation in adipose tissue. Dec 15, 2003 obesityinduced inflammatory changes in adipose tissue kathryn e. B activation by combining implantation of 3t3l1 preadipocytes and in vivo bli technique. The causal link between obesity and these pathologies has recently been identified as chronic lowgrade systemic.
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. Obesityinduced changes in adipose tissue microenvironment and. Tolllike receptor 2 and 4 43 overview of tolllike receptors 43 tlr4 and tlr2 induced inflammation and. This inflammatory trait is associated with insulin resistance and subsequently type 2 diabetes mellitus.
Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Metabolic changes in these cells also contributed to the. Louis, missouri, united states of america, 2department of histology and. Changes in adipose tissue immune status affect its cytokine content and consequently adipocyte metabolism and insulin sensitivity.
Obesityinduced adipose tissue inflammation and insulin resistance, role of the adipocyte in development of type 2 diabetes, coleen croniger, intechopen, doi. Adipose tissueresident immune cells in obesity and. Regulation of obesityinduced adipose tissue inflammation. Body mass indexindependent inflammation in omental. Diet rich in saturated fat, transfats, or refined sugar is associated with higher production of pro inflammatory molecules smoking. Obesity is an energyrich condition associated with overnutrition, which impairs systemic metabolic homeostasis and elicits stress.
Adapting to obesity with adipose tissue inflammation. Shaw1,3 1department of pathology and immunology, washington university school of medicine, st. In particular, invariant natural killer t inkt cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesityinduced in. Lifespan extension drug interventions affect adipose. Obesity induced changes in adipose tissue fatty acid metabolism 33 obesity induced cytokine production in adipose tissue 36 obesity induced macrophage accumulation in adipose tissue 40 obesity induced inflammation and insulin resistance. Lifespan extension drug interventions affect adipose tissue. Hotamisligil department of genetics and complex diseases, harvard school of public health, boston. Osteopontin mediates obesityinduced adipose tissue macrophage infiltration and insulin resistance in mice takashi nomiyama,1 diego pereztilve,2 daisuke ogawa,1 florence gizard, 1 yue zhao, elizabeth b. Osteopontin mediates obesityinduced adipose tissue macrophage infiltration and insulin resistance in mice takashi nomiyama,1 diego pereztilve,2 daisuke ogawa,1 florence gizard, 1 yue zhao. Human adipose tissue accumulation is associated with pro. The findings of macrophage infiltration in adipose tissue provide a mechanistic insight into the obesityinduced lowgrade inflammation. Systemic inflammatory changes lowgrade systemic inflammatory state production and secretion of adipocytokines involved in oa development obesity comorbidities hypertension, impaired glucose.
Osteopontin mediates obesityinduced adipose tissue. Adipocytes become hypertrophic and immune cells, such as macrophages 3,4, t and bcells, infiltrate into the adipose tissue. It also activates an inflammatory process in metabolically active sites. Of particular note, xu et al 51 reported that the increased expression of inflammationspecific genes by macrophages in the adipose tissue of obese mice preceded. As consequence, increased circulating levels of proinflammatory cytokines, hormonelike molecules, and other inflammatory markers are. Obesityinduced inflammatory changes in adipose tissue ncbi. Adipose tissue is considered an endocrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. Obesityinduced changes in adipose tissue fatty acid metabolism 33 obesityinduced cytokine production in adipose tissue 36 obesityinduced macrophage accumulation in adipose tissue 40. Obesity leads to an increased risk for type 2 diabetes, heart disease, stroke, and cancer. Deletion of cd1d in adipocytes aggravates adipose tissue. Obesityinduced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple. Role of nkg2d in obesityinduced adipose tissue inflammation. In this study, a high fat diet was found to significantly aggravate colitis induced by dextran sulfate sodium dss. Earlier transcriptional profiling experiments performed in adipose tissue from lean and obese animal models, or following treatment of obese animals with members.
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 this study, we developed an animal model to evaluate and monitor obesityinduced chronic, lowgrade inflammation in adipose tissue through nf. Pdf obesityinduced dna released from adipocytes stimulates. Nk cells link obesityinduced adipose stress to inflammation. This group proposed that various obesity induced mediators e.
Antiinflammatory nutrition as a pharmacological approach to treat obesity. 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. Dysregulation of acute inflammation failure to remove causative agent virus, protozoa, fungi, toxins, foreign materials. Visceral obesity has been demonstrated to be associated with macrophage infiltration and inflammation in adipose tissue. The roles of adipokines, proinflammatory cytokines, and. Obesity is associated with a state of chronic, lowgrade inflammation. An important early event in vat inflammation is the activation of macrophages in adipose. Events initiating obesityinduced adipose tissue inflammation. Two manuscripts in this issue of the jci see the related. Differential role of adipose tissues in obesity and related.
The findings of macrophage infiltration in adipose tissue provide a mechanistic insight into the obesity induced lowgrade inflammation. Tissue immune cells fuel obesityassociated inflammation frontiers. These changes contribute to adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death. Mar 25, 2020 in this study, we determined changes in liver and adipose tissue transcriptomes of a porcine model for prepubertal early obesity induced by a highcalorie diet and supplemented with bioactive. However, how adipose tissue stress is translated into a signal that activates the immune system is largely unknown. Efficient targeting of adipose tissue macrophages in. Lipoxin a4 attenuates obesityinduced adipose inflammation. Meanwhile, a high fat diet changed the mirna profile of the visceral adipose exosomes, switching the exosomes from anti inflammatory to a pro inflammatory phenotype. Obesity and the role of adipose tissue in inflammation and. Lipoxina4 and a synthetic lipoxin analog protected against obesityinduced kidney and liver disease. Macrophage recruitment to adipose tissue is a hallmark of obesity and can contribute to insulin resistance.
Morphological and inflammatory changes in visceral adipose. With age, the changes in rodent and human adipose tissue distribution and mass lead to an ageassociated form of obesity 12,1618. Adapting to obesity with adipose tissue inflammation nature. Natural killer t cells are involved in adipose tissues. The role of adipose tissue and adipokines in obesityrelated. Their metabolic role changes as they enlarge with increasing obesity. Obesity is associated with lowgrade chronic inflammation. Obese adipose tissue is characterized by inflammation and progressive infiltration by macrophages as obesity develops 10, 11. These spx induced changes were inhibited by systemic administration of il10. These studies prompt consideration of new models to include a major role for macrophages in the molecular changes that occur in adipose tissue. Dietary intake of bioactive ingredients impacts liver and. Lipoxins mediated protection by decreasing adipose inflammation and promoting a macrophage m1tom2 switch.
Body mass indexindependent inflammation in omental adipose. The role of adipose tissue immune cells in obesity and lowgrade. An important early event in vat inflammation is the activation of macrophages in adipose tissue. As the association of obesity to proinflammatory changes has been repeatedly proven, it is reasonable to assume that the macrophage. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation.
Adipose tissue immune cells in obesityassociated inflammation. Differential role of adipose tissues in obesity and. Obesity is accompanied by a chronic inflammation of adipose tissue, and this. We sought to identify the molecular pathways that might cause obesity associated insulin resistance in humans by studying the morbidly obese who were insulin sensitive versus insulin resistant, thereby. Chronic nutrient excess leads to visceral adipose tissue vat expansion and dysfunction in an active process that involves the adipocytes, their supporting matrix, and immune cell infiltrates.
Spx aggravated the inflammatory response in white adipose tissue wat and the liver and suppressed adiposity in wat. Visceral adipose tissue derived exosomes exacerbate. The complex immunological and inflammatory network of adipose tissue in obesity. Efficient targeting of adipose tissue macrophages in obesity. Furthermore, inflammatory cytokine expression in epididymal adipose tissue increased in the absence of rapainduced fat mass changes. Moreover, spx had little effect on the inflammatory responses in wat and the liver of il10ko mice. To get insight into molecular mechanisms underlying insulin resistance, we compared acute in vivo effects of insulin on adipose tissue transcriptional profiles between obese insulin. Obesityinduced adipose tissue inflammation and insulin.
Pdf obesityinduced inflammatory changes in adipose tissue. In fact, adipose tissue macrophages are responsible for almost all adipose tissue tnf. In addition, the adipose tissue macrophages in dietinduced obesity tend to have a proinflammatory m1 phenotype, involving il6, il12, and tnf 51. Causes localized inflammation and lowers production of anti inflammatory molecules.
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