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. Dec 15, 2003 obese adipose tissue is characterized by inflammation and progressive infiltration by macrophages as obesity develops 10, 11. In human obesity, the stroma vascular fraction svf of white adipose tissue wat is enriched in macrophages. This inflammatory trait is associated with insulin resistance and subsequently type 2 diabetes mellitus. Morphological and inflammatory changes in visceral adipose.
Obesityinduced insulin resistance is a major risk factor for type 2 diabetes, hyperlipidemia, cardiovascular disease, and some types of cancer 1 3. Lipoxinmediated protection was adiponectin independent, but correlated with restored adipose. The complex immunological and inflammatory network of adipose tissue in obesity. Their metabolic role changes as they enlarge with increasing obesity. With age, the changes in rodent and human adipose tissue distribution and mass lead to an ageassociated form of obesity 12,1618. Visceral adipose tissue derived exosomes exacerbate. These spx induced changes were inhibited by systemic administration of il10. B activation by combining implantation of 3t3l1 pre. Adipose tissue immune cells in obesityassociated inflammation. It also activates an inflammatory process in metabolically active sites, such as white adipose tissue, liver, and immune cells. Moreover, spx had little effect on the inflammatory responses in wat and the liver of il10ko mice. Dysregulation of acute inflammation failure to remove causative agent virus, protozoa, fungi, toxins, foreign materials. 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.
Tolllike receptor 2 and 4 43 overview of tolllike receptors 43 tlr4 and tlr2 induced inflammation and. Hotamisligil published december 15, 2003 citation information. Lipoxins mediated protection by decreasing adipose inflammation and promoting a macrophage m1tom2 switch. Two manuscripts in this issue of the jci see the related articles. The findings of macrophage infiltration in adipose tissue provide a mechanistic insight into the obesity induced lowgrade inflammation. Spx aggravated the inflammatory response in white adipose tissue wat and the liver and suppressed adiposity in wat. The roles of adipokines, proinflammatory cytokines, and. Body mass indexindependent inflammation in omental. 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. Adipose tissue, inflammation and cardiovascular disease scielo.
In vivo imaging of obesityinduced inflammation in adipose. Diet rich in saturated fat, transfats, or refined sugar is associated with higher production of pro inflammatory molecules smoking. These changes contribute to adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death. The accumulation in adipose tissue of macrophages in an inflammatory state is a hallmark of obesityinduced insulin resistance. Obesity is an energyrich condition associated with overnutrition, which impairs systemic metabolic homeostasis and elicits stress. In fact, adipose tissue macrophages are responsible for almost all adipose tissue tnf. Obesity and the role of adipose tissue in inflammation and. Differential role of adipose tissues in obesity and. Obesityinduced changes in their number and activity result in the activation of local and later systemic inflammatory response, marking the transition from simple. 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. 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. Deletion of cd1d in adipocytes aggravates adipose tissue.
Furthermore, the adipocytes in individuals who are obese. Obesityinduced inflammatory changes in adipose tissue ncbi. In addition, the adipose tissue macrophages in dietinduced obesity tend to have a proinflammatory m1 phenotype, involving il6, il12, and tnf 51. Tlr3 is present in human adipocytes, but its signalling. Jun 15, 2011 obesity is associated with lowgrade chronic inflammation. Pdf obesityinduced inflammatory changes in adipose tissue. Two manuscripts in this issue of the jci see the related.
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. 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. Development of obesityinduced inflammation and insulin. Obesity induced adipose tissue inflammation and insulin resistance, role of the adipocyte in development of type 2 diabetes, coleen croniger, intechopen, doi.
Changes in adipocyte and fat pad size lead to physical changes in the surrounding area and modifications of the paracrine function of the adipocyte. 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. 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. Lifespan extension drug interventions affect adipose. Lifespan extension drug interventions affect adipose tissue. Obesityinduced dna released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance article pdf available in science advances 23. Obese adipose tissue is characterized by inflammation and progressive infiltration by macrophages as obesity develops 10, 11.
A novel antiinflammatory role for spleenderived interleukin. 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. The causal link between obesity and these pathologies has recently been identified as chronic lowgrade systemic. The findings of macrophage infiltration in adipose tissue provide a mechanistic insight into the obesityinduced lowgrade inflammation. Targeting inflammationinduced obesity and metabolic. In vivo imaging of obesityinduced inflammation in adipose tissue. Adipose tissue is considered an endocrine organ that secretes various adipokines involved in metabolic regulation and inflammatory processes. Furthermore, inflammatory cytokine expression in epididymal adipose tissue increased in the absence of rapainduced fat mass changes. Adipose tissue gene expression analysis reveals changes in. Osteopontin mediates obesityinduced adipose tissue. Adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Omental adipose tissue released 23 times more il6 than did sc adipose tissue. The role of adipose tissue and adipokines in 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.
Pdf obesityinduced dna released from adipocytes stimulates. The seminal finding that the expression of a proinflammatory cytokine, tumor necrosis factor. Aug 11, 2017 adipose tissue inflammation is an adaptive response to overnutrition in the early stages of obesity, but later becomes maladaptive. Role of nkg2d in obesityinduced adipose tissue inflammation and insulin resistance junjae chung1, mary a. Obesityinduced inflammatory changes in adipose tissue kathryn e. Pdf obesity is associated with a state of chronic, lowgrade inflammation. Hotamisligil department of genetics and complex diseases, harvard school of public health, boston. Body mass indexindependent inflammation in omental adipose. It is increasingly accepted that chronic inflammation is a feature of obesity. Under lean conditions, adipose tissueresident macrophages have an antiinflammatory m2like phenotype. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women. Adipose tissue is not only a reservoir for energy, but also an immune organ.
Louis, missouri, united states of america, 2department of histology and. Jci obesityinduced inflammatory changes in adipose tissue. Modulation of obesityinduced inflammation by dietary fats. Development of obesity leads to morphological and functional changes in adipose tissue. Tissue immune cells fuel obesityassociated inflammation frontiers. 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 leads to an increased risk for type 2 diabetes, heart disease, stroke, and cancer. The role of adipose tissue immune cells in obesity and lowgrade. Nk cells link obesityinduced adipose stress to inflammation. Dietary intake of bioactive ingredients impacts liver and.
Regulation of obesityinduced adipose tissue inflammation. Role of nkg2d in obesityinduced adipose tissue inflammation. Lipoxina4 and a synthetic lipoxin analog protected against obesityinduced kidney and liver disease. 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.
In particular, invariant natural killer t inkt cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesityinduced in. Systemic inflammatory changes lowgrade systemic inflammatory state production and secretion of adipocytokines involved in oa development obesity comorbidities hypertension, impaired glucose. Differential role of adipose tissues in obesity and related. Depending on their phenotype, macrophages can be designated either as pro. The role of adipose tissue and adipokines in obesityrelated. Thus, these studies also suggest that ginger has potential in preventing obesity and obesitylinked metabolic effects. Dec 15, 2003 obesityinduced inflammatory changes in adipose tissue kathryn e. As consequence, increased circulating levels of proinflammatory cytokines, hormonelike molecules, and other inflammatory markers are. Adapting to obesity with adipose tissue inflammation. An important early event in vat inflammation is the activation of macrophages in adipose tissue. The causal link between obesity and these pathologies has recently been identified as chronic lowgrade systemic inflammation initiated by pro inflammatory macrophages in visceral adipose tissue. Shaw1,3 1department of pathology and immunology, washington university school of medicine, st. Adipocytes become hypertrophic and immune cells, such as macrophages 3,4, t and bcells. Obesity, adipose tissue, inflammation and update on obesity.
It also activates an inflammatory process in metabolically active sites. Adipose tissues secrete bioactive substances, referred to as adipokines, which largely function as modulators of inflammation. In this study, we developed an animal model to evaluate and monitor obesityinduced chronic, lowgrade inflammation in adipose tissue through nf. Changes in adipose tissue immune status affect its cytokine content and consequently adipocyte metabolism and insulin sensitivity. Causes localized inflammation and lowers production of anti inflammatory molecules. 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. Obesity induced inflammatory changes in adipose tissue. This obesity induced inflammatory state involves a phenotypic switch in adipose tissue macrophage from m2 to m1 state 23, 24. Obesityinduced adipose tissue inflammation and insulin resistance, role of the adipocyte in development of type 2 diabetes, coleen croniger, intechopen, doi. Obesity is accompanied by a chronic inflammation of adipose tissue, and this. Macrophage recruitment to adipose tissue is a hallmark of obesity and can contribute to insulin resistance. Obesityinduced changes in adipose tissue microenvironment and. Isolated adipocytes prepared from these tissues also released il6 omental sc, but this accounted for only 10%.
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. In this study, a high fat diet was found to significantly aggravate colitis induced by dextran sulfate sodium dss. Adipose tissueresident immune cells in obesity and. Efficient targeting of adipose tissue macrophages in. Obesityinduced inflammatory changes in adipose tissue.
Obesityinduced adipose tissue inflammation and insulin. Antiinflammatory nutrition as a pharmacological approach to treat obesity. In addition, the adipose tissue macrophages in diet induced obesity tend to have a pro inflammatory m1 phenotype, involving il6, il12, and tnf 51. These cells may contribute to lowgrade inflammation and to its metabolic. Efficient targeting of adipose tissue macrophages in obesity. Adapting to obesity with adipose tissue inflammation nature. 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.
Earlier transcriptional profiling experiments performed in adipose tissue from lean and obese animal models, or following treatment of obese animals with members. Metabolic changes in these cells also contributed to the. This group proposed that various obesity induced mediators e. Events initiating obesityinduced adipose tissue inflammation. Deep sequencing of the transcriptome reveals inflammatory.
These studies prompt consideration of new models to include a major role for macrophages in the molecular changes that occur in adipose tissue. Innate immunity plays a pivotal role in obesityinduced lowgrade inflammation originating from adipose tissue. Obesity is associated with a state of chronic, lowgrade inflammation. Visceral obesity has been demonstrated to be associated with macrophage infiltration and inflammation in adipose tissue. Obesity, adipose tissue, inflammation and update on. Human adipose tissue accumulation is associated with pro. Natural killer t cells are involved in adipose tissues. Blocking il6 transsignaling prevents highfat dietinduced. Obesity is associated with lowgrade chronic inflammation. Obesity is a strong risk factor for resistance to insulinmediated glucose disposal, a precursor of type 2 diabetes and other disorders. Tlr3 is present in human adipocytes, but its signalling is.
Key receptors of the innate immune system including tolllike receptors2 and 4 tlrs are. Obesity and the role of adipose tissue in inflammation and metabolism andrew s greenberg. However, how adipose tissue stress is translated into a signal that activates the immune system is largely unknown. 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. A pioneering epidemic study has revealed a strong association between obesity and the risk of colitis. This group proposed that various obesityinduced mediators e. As the association of obesity to proinflammatory changes has been repeatedly proven, it is reasonable to assume that the macrophage. Obesityinduced changes in adipose tissue fatty acid metabolism 33 obesityinduced cytokine production in adipose tissue 36 obesityinduced macrophage accumulation in adipose tissue 40. Lipoxin a4 attenuates obesityinduced adipose 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. Adipocytes become hypertrophic and immune cells, such as macrophages 3,4, t and bcells, infiltrate into the adipose tissue. 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. B activation by combining implantation of 3t3l1 preadipocytes and in vivo bli technique.