Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

Tao, Tao; Li, Shengxian; Zhao, Aimin; Zhang, Yanyun; Liu, Wei

doi:10.1530/eje-12-0340

Cited by 20 publications

(18 citation statements)

References 39 publications

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“…Moreover, CD11c mRNA abundance made a stronger contribution to models predicting TNFa, which has proinflammatory properties that might significantly contribute to the pathogenesis of insulin resistance in PCOS women (133).…”

Section: Obesity Body Composition and Nutritionmentioning

confidence: 99%

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

European Journal of Endocrinology

568

492

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Polycystic ovary syndrome (PCOS) is the most common ovarian disorder associated with androgen excess in women, which justifies the growing interest of endocrinologists. Great efforts have been made in the last 2 decades to define the syndrome. The presence of three different definitions for the diagnosis of PCOS reflects the phenotypic heterogeneity of the syndrome. Major criteria are required for the diagnosis, which in turn identifies different phenotypes according to the combination of different criteria. In addition, the relevant impact of metabolic issues, specifically insulin resistance and obesity, on the pathogenesis of PCOS, and the susceptibility to develop earlier than expected glucose intolerance states, including type 2 diabetes, has supported the notion that these aspects should be considered when defining the PCOS phenotype and planning potential therapeutic strategies in an affected subject. This paper offers a critical endocrine and European perspective on the debate on the definition of PCOS and summarises all major aspects related to aetiological factors, including early life events, potentially involved in the development of the disorder. Diagnostic tools of PCOS are also discussed, with emphasis on the laboratory evaluation of androgens and other potential biomarkers of ovarian and metabolic dysfunctions. We have also paid specific attention to the role of obesity, sleep disorders and neuropsychological aspects of PCOS and on the relevant pathogenetic aspects of cardiovascular risk factors. In addition, we have discussed how to target treatment choices based according to the phenotype and individual patient's needs. Finally, we have suggested potential areas of translational and clinical research for the future with specific emphasis on hormonal and metabolic aspects of PCOS.

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Section: Obesity Body Composition and Nutritionmentioning

confidence: 99%

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Conway¹,

Dewailly²,

Diamanti-Kandarakis³

et al. 2014

European Journal of Endocrinology

568

492

View full text Add to dashboard Cite

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“…Among these, the existence of proinflammatory genotypes has been suggested, including polymorphisms of sequences codifying TNF, TNF receptor, IL-6, and IL-10 [ 148 ]. Remarkably, greater expression of the CD11c gene is associated with greater proinflammatory macrophage infiltration is SAT and VAT, favoring a transition to decreased secretion of adiponectin and increased TNF and leptin secretion from adipocytes [ 149 ].…”

Section: Chronic Inflammation: From Insulin Resistance To Polycystmentioning

confidence: 99%

Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

Rojas

Chávez-Castillo

Olivar

et al. 2014

International Journal of Reproductive Medicine

319

270

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Polycystic ovary syndrome (PCOS) is a highly prevalent endocrine-metabolic disorder that implies various severe consequences to female health, including alarming rates of infertility. Although its exact etiology remains elusive, it is known to feature several hormonal disturbances, including hyperandrogenemia, insulin resistance (IR), and hyperinsulinemia. Insulin appears to disrupt all components of the hypothalamus-hypophysis-ovary axis, and ovarian tissue insulin resistance results in impaired metabolic signaling but intact mitogenic and steroidogenic activity, favoring hyperandrogenemia, which appears to be the main culprit of the clinical picture in PCOS. In turn, androgens may lead back to IR by increasing levels of free fatty acids and modifying muscle tissue composition and functionality, perpetuating this IR-hyperinsulinemia-hyperandrogenemia cycle. Nonobese women with PCOS showcase several differential features, with unique biochemical and hormonal profiles. Nevertheless, lean and obese patients have chronic inflammation mediating the long term cardiometabolic complications and comorbidities observed in women with PCOS, including dyslipidemia, metabolic syndrome, type 2 diabetes mellitus, and cardiovascular disease. Given these severe implications, it is important to thoroughly understand the pathophysiologic interconnections underlying PCOS, in order to provide superior therapeutic strategies and warrant improved quality of life to women with this syndrome.

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“…Murine ATM have been primarily defined as F4/80 + CD11b + and with obesity F4/80 + CD11b + CD11c + ATM accumulate (9, 12). The importance of CD11c + ATM has been emphasized in numerous studies in mice and humans (6, 12, 13). Obesity induces CD11c expression in macrophages and circulating monocytes to enhance their trafficking into adipose tissue (14).…”

Section: Introductionmentioning

confidence: 99%

Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance

Cho

Zamarron

Muir

et al. 2016

The Journal of Immunology

122

155

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Dynamic changes of adipose tissue leukocytes, including adipose tissue macrophage (ATM) and adipose tissue dendritic cells (ATDC) contribute to obesity-induced inflammation and metabolic disease. However, clear discrimination between ATDC and ATM in adipose tissue has limited progress in the field of immunometabolism. In this study, we utilize CD64 to distinguish ATM and ATDC and investigated the temporal and functional changes in these myeloid populations during obesity. Flow cytometry and immunostaining demonstrated that the definition of ATM as F4/80+CD11b+ cells overlaps with other leukocytes and that CD45+CD64+ is specific for ATM. The expression of core DC genes were enriched in CD11c+CD64− cells (ATDC), while core macrophage genes were enriched in CD45+CD64+ cells (ATM). CD11c+CD64− ATDC expressed MHCII and co-stimulatory receptors and had similar capacity to stimulate CD4+ T cell proliferation as ATM. ATDC were predominantly CD11b+ conventional DCs and made up the bulk of CD11c+ cells in adipose tissue with moderate high fat diet exposure. Mixed chimeric experiments with Ccr2−/− mice demonstrated that high-fat diet (HFD) induced ATM accumulation from monocytes was dependent on CCR2; while ATDC accumulation was less CCR2-dependent. ATDC accumulation during obesity was attenuated in Ccr7−/− mice and was associated with decreased adipose tissue inflammation and insulin resistance. CD45+CD64+ ATM and CD45+CD64−CD11c+ ATDC were identified in human obese adipose tissue and ATDC were increased in subcutaneous adipose tissue compared to omental. These results support a revised strategy for unambiguous delineation of ATM and ATDC and suggests that ATDC are independent contributors to adipose tissue inflammation during obesity.

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Expression of the CD11c gene in subcutaneous adipose tissue is associated with cytokine level and insulin resistance in women with polycystic ovary syndrome

Cited by 20 publications

References 39 publications

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

The polycystic ovary syndrome: a position statement from the European Society of Endocrinology

Polycystic Ovary Syndrome, Insulin Resistance, and Obesity: Navigating the Pathophysiologic Labyrinth

Adipose Tissue Dendritic Cells Are Independent Contributors to Obesity-Induced Inflammation and Insulin Resistance

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