Adipose tissues as an ancestral immune organ: Site‐specific change in obesity

Ishimori

et al. 2010

ATVB

187

151

Background-Macrophage and lymphocyte infiltration in adipose tissue may contribute to the pathogenesis of obesity-mediated metabolic disorders. Natural killer T (NKT) cells, which integrate proinflammatory cytokines, have been demonstrated in the atherosclerotic lesions and in visceral adipose tissue. Objective-To determine whether NKT cells are involved in glucose intolerance and adipose tissue inflammation in diet-induced obese mice. Methods and Results-To determine whether NKT cells are involved in the development of glucose intolerance, male ␤ 2 -microglobulin knockout (KO) mice lacking NKT cells and C57BL/6J (wild-type) mice were fed with a high-fat diet (HFD) for 13 weeks. Body weight and visceral obesity were comparable between wild-type and KO mice. However, macrophage infiltration was reduced in adipose tissue and glucose intolerance was significantly ameliorated in KO mice.To further confirm that NKT cells are involved in these abnormalities, ␣-galactosylceramide, 0.1 g/g body weight, which specifically activates NKT cells, was administered after 13 weeks of HFD feeding. ␣-Galactosylceramide significantly exacerbated glucose intolerance and macrophage infiltration as well as cytokine gene expression in adipose tissue. O besity, specifically visceral obesity, increases the risk for metabolic disorders, such as type 2 diabetes mellitus, dyslipidemia, and hypertension as well as atherosclerotic cardiovascular diseases. Previous studies have demonstrated that the accumulation of macrophages within adipose tissue is well documented in obese individuals and that adipose tissue inflammation plays an important role in the pathogenesis of these metabolic disorders. 1,2 Macrophages are attracted by chemokines, such as monocyte chemoattractant protein 1 (MCP-1), and contribute to local inflammation through the release of other inflammatory cytokines, such as tumor necrosis factor (TNF) ␣. In high-fat diet (HFD)-fed obese mice, it has been shown that infiltration of macrophages into adipose tissue coincides with the occurrence of obesitymediated metabolic disorders. 2 The important role of adipose tissue macrophages in the pathogenesis of metabolic disorders has further been supported by recent data in C-C motif chemokine receptor 2 (CCR2)-deficient mice. 3 The CCR2 Ϫ/Ϫ mice exhibited a reduction in adipose tissue macrophages in association with an improvement of glucose homeostasis and insulin sensitivity. However, the abolished monocyte and macrophage recruitment into peripheral tissue via interaction with MCP-1 could not completely inhibit HFD-mediated metabolic disorders, suggesting that other inflammatory cells may play a role in this context. Wu et al 4 and Rocha et al 5 demonstrated that CD3-positive T lymphocytes are present in human adipose tissue; and regulated upon activation, normal T cell expressed secreted (RANTES), a T-cell-specific chemokine, and its respective receptor CCR5 are expressed in adipose tissue from obese patients. However, the role of other types of lymphocytes in adipose tissue inflam...

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Natural Killer T Cells Are Involved in Adipose Tissues Inflammation and Glucose Intolerance in Diet-Induced Obese Mice

Ishimori

et al. 2010

ATVB

187

151

“…In contrast to ,2% of all lymphocytes in blood or lymph nodes being NK or NKT cells, these cells account for ,12% in inguinal fat and exceed 30% in the epididymal fat pad. 95 Although their presence may explain the low cancer rates in adipose tissue, there is no prominent epididymal fat pad in the human, as there is in laboratory rodents, and no attention has been paid to any adipose tissues adhering tightly over the caput and corpus.…”

Section: Endogenous Barriers To Tumour Formation: Immunosurveillancementioning

confidence: 99%

Why are epididymal tumours so rare?

Yeung¹,

Wang²,

Cooper³

2012

Asian J Androl

Epididymal tumour incidence is at most 0.03% of all male cancers. It is an enigma why the human epididymis does not often succumb to cancer, when it expresses markers of stem and cancer cells, and constitutively expresses oncogenes, pro-proliferative and pro-angiogenic factors that allow tumour cells to escape immunosurveillance in cancer-prone tissues. The privileged position of the human epididymis in evading tumourigenicity is reflected in transgenic mouse models in which induction of tumours in other organs is not accompanied by epididymal neoplasia. The epididymis appears to: (i) prevent tumour initiation (it probably lacks stem cells and has strong anti-oxidative mechanisms, active tumour suppressors and inactive oncogene products); (ii) foster tumour monitoring and destruction (by strong immuno-surveillance and -eradication, and cellular senescence); (iii) avert proliferation and angiogenesis (with persistent tight junctions, the presence of anti-angiogenic factors and misplaced pro-angiogenic factors), which together (iv) promote dormancy and restrict dividing cells to hyperplasia. Epididymal cells may be rendered non-responsive to oncogenic stimuli by the constitutive expression of factors generally inducible in tumours, and resistant to the normal epididymal environment, which mimics that of a tumour niche promoting tumour growth. The threshold for tumour initiation may thus be higher in the epididymis than in other organs. Several anti-tumour mechanisms are those that maintain spermatozoa quiescent and immunologically silent, so the low incidence of cancer in the epididymis may be a consequence of its role in sperm maturation and storage. Understanding these mechanisms may throw light on cancer prevention and therapy in general.

“…14,16 The adipose tissue is highly complex and is constituted by mature adipocytes, preadipocytes, fibroblasts, vascular smooth muscle cells, endothelial cells, monocytes, and macrophages, 18 and lymphocytes. 19 There is confusion in the scientific literature about the terms used to describe multipotent stem cells of adipose tissue, such as ADSC, human processed lipoaspirate (PLA) cells, preadipocytes or SVF. The acronym SVF corresponds to ADSC and describes the cells obtained immediately after the digestion of collagenase.…”

Section: Introductionmentioning

confidence: 99%

Células-tronco derivadas de tecido adiposo humano: desafios atuais e perspectivas clínicas

Yarak

Okamoto

2010

An. Bras. Dermatol.

Adult or somatic stem cells hold great promise for tissue regeneration. Currently, one major scientific interest is focused on the basic biology and clinical application of mesenchymal stem cells. Adipose tissue-derived stem cells share similar characteristics with bone marrow mesenchymal stem cells, but have some advantages including harvesting through a less invasive surgical procedure. Moreover, adipose tissue-derived stem cells have the potential to differentiate into cells of mesodermal origin, such as adipocytes, cartilage, bone, and skeletal muscle, as well as cells of non-mesodermal lineage, such as hepatocytes, pancreatic endocrine cells, neurons, cardiomyocytes, and vascular endothelial cells. There are, however, inconsistencies in the scientific literature regarding methods for harvesting adipose tissue and for isolating, characterizing and handling adipose tissue-derived stem cells. Future clinical applications of adipose tissue-derived stem cells rely on more defined and widespread methods for obtaining cells of clinical grade quality. In this review, current methods in adipose tissue-derived stem cell research are discussed with emphasis on strategies designed for future applications in regenerative medicine and possible challenges along the way. Key words: Adipocytes; Adipose tissue; Adult stem cells; Tissue therapy Resumo: As células-tronco adultas ou somáticas detêm grande promessa para a reparação e regeneração de tecidos. Atualmente, o interesse dos cientistas é contínuo na investigação da biologia de células-tronco mesenquimais, tanto em aspectos básicos, quanto no potencial de aplicações terapêuticas. As células-tronco adultas derivadas do estroma do tecido adiposo, em comparação com as células-tronco derivadas do estroma da medula óssea, apresentam como vantagem o método fácil de obtenção da fonte tecidual. As células-tronco adultas derivadas do estroma do tecido adiposo apresentam potencial para se diferenciarem em células de tecidos mesodérmicos, como os adipócitos, as cartilagens, os ossos e o músculo esquelético e não mesodérmicos, como os hepatócitos, as células pancreáticas endócrinas, os neurônios, os hepatóci-tos e as células endoteliais vasculares. Entretanto, os dados disponíveis na literatura científica sobre as características das células-tronco adultas derivadas do estroma do tecido adiposo e os procedimentos para sua obtenção e manipulação no laboratório são inconsistentes. É necessário o desenvolvimento de metodologias e procedimentos eficazes de isolamento dessas células para obtenção de células em quantidade e qualidade suficientes para aplicação terapêutica. Nesta revisão, são discutidos os métodos correntes de coleta de tecido adiposo, isolamento e caracterização de células-tronco adultas derivadas do estroma do tecido adiposo, com ênfase na futura aplicação em medicina regenerativa e nos possíveis desafios nesse recente campo da ciência.