Serum tumor necrosis factor-α levels and components of the metabolic syndrome in obese adolescents

Moon, Yoo Sun; Kim, Do-Hoon; Song, Dong‐Keun

doi:10.1016/j.metabol.2004.02.007

Cited by 112 publications

(97 citation statements)

References 34 publications

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“…Levels fourfold higher were observed in insulinresistant obese humans compared with healthy humans (32). Obese adolescents have been shown to exhibit higher TNF-␣ and its soluble receptor concentrations than nonobese ones, and TNF-␣ concentration has been positively correlated with several components of metabolic syndrome in obese adolescents (33). These results suggest that this cytokine could be an early marker of the inflammatory state predisposing to metabolic syndrome development during childhood.…”

Section: Conclusion -In This Article Wementioning

confidence: 86%

A Prospective Study on the Prevalence of Metabolic Syndrome Among Healthy French Families

et al. 2005

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OBJECTIVE -The purpose of this study was to estimate the longitudinal variation of prevalence of metabolic syndrome within French families and to observe biological parameters involved in cardiovascular disease among their offspring.RESEARCH DESIGN AND METHODS -Three hundred seventy-one apparently healthy families (1,366 individuals) taken from the STANISLAS cohort were studied. The subjects were examined at two time points with a 5-year interval (t 0 and t ϩ5 ). The crude prevalence of metabolic syndrome was assessed among parents according to the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP) definition.RESULTS -The prevalence of metabolic syndrome was 5.9% in men and 2.1% in women at t 0 , rising to 7.2 and 5.4% in men and women, respectively, at t ϩ5 . Children of parents having metabolic syndrome showed higher levels of tumor necrosis factor-␣ (TNF-␣), whereas their HDL cholesterol and apolipoprotein (apo) E concentrations were lower compared with those of age-and sex-matched control subjects (P Յ 0.05). When applying NCEP ATP definitions that included either antihypertensive drugs only or all the drugs involved in metabolic syndrome, we found that the three parameters shared by the three different versions of the definition were TNF-␣, HDL cholesterol, and an interaction between alcohol consumption and parental metabolic syndrome on HDL cholesterol concentration.CONCLUSIONS -Metabolic syndrome increases with age in supposedly healthy families from the STANISLAS cohort. In offspring of affected people, it seems to be predictive of higher values of TNF-␣ and low HDL cholesterol levels, which are two major cardiovascular factors. Therefore, in terms of prevention, it is important to identify and follow subjects with metabolic syndrome as well as their offspring, even in apparently healthy populations, to enable early disease management. Diabetes Care 28:675-682, 2005

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Section: Conclusion -In This Article Wementioning

confidence: 86%

A Prospective Study on the Prevalence of Metabolic Syndrome Among Healthy French Families

et al. 2005

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“…Recent studies have suggested that activity of TACE/ ADAM-17 or its inhibitor, Timp3, may be altered in humans affected by chronic metabolic and inflammatory diseases because of the observation of increased circulating levels of soluble forms of TACE substrates like TNF-␣, soluble TNF receptor-1, and soluble IL-6 receptor (12)(13)(14). Inhibition of TACE by KB-R775 led to improved insulin sensitivity in a rat model of type 2 diabetes (15).…”

Section: Discussionmentioning

confidence: 99%

“…To assess the role of TACE in the development of obesity and its complications, Tace ϩ/Ϫ mice and wild-type littermates, fed a standard laboratory diet or an HFD, were used because Tace-null mice survive only a few days after delivery due to severe developmental defects (12). Under standard diet conditions, weight gain was comparable in the two mouse models, but Tace ϩ/Ϫ mice were significantly protected from obesity induced by an HFD (Fig.…”

Section: Tacementioning

confidence: 99%

Mice Heterozygous for Tumor Necrosis Factor-α Converting Enzyme Are Protected From Obesity-Induced Insulin Resistance and Diabetes

et al. 2007

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OBJECTIVE-Tumor necrosis factor (TNF)-␣ is known to affect insulin sensitivity, glucose, and lipid metabolism through alternative and redundant mechanisms at both translational and post-translational levels. TNF-␣ exerts its paracrine effects once the membrane-anchored form is shed and released from the cell membrane. TNF-␣ cleavage is regulated by TNF-␣ converting enzyme (TACE), which regulates the function of several transmembrane proteins, such as interleukin-6 receptor and epidermal growth factor receptor ligands. The role of TACE in high-fat diet (HFD)-induced obesity and its metabolic complications is unknown.RESEARCH DESIGN AND METHODS-To gain insights into the role of TACE in metabolic disorders, we used Tace ϩ/Ϫ mice fed a standard or high-fat diet for 16 weeks. RESULTS-We observed that Taceϩ/Ϫ mice are relatively protected from obesity and insulin resistance compared with wildtype littermates. When fed an HFD, wild-type mice exhibited visceral obesity, increased free fatty acid and monocyte chemoattractant protein (MCP)1 levels, hypoadiponectinemia, glucose intolerance, and insulin resistance compared with Tace ϩ/Ϫ mice. Interestingly, Tace ϩ/Ϫ mice exhibited increased uncoupling protein-1 and GLUT4 expression in white adipose tissue. CONCLUSIONS-Our results suggest that modulation of TACE activity is a new pathway to be investigated for development of agents acting against obesity and its metabolic complications. Diabetes 56:2541-2546, 2007 S everal studies have suggested that obesity progressively leads to the recruitment of monocyte/ macrophage in the visceral adipose tissue, thus initiating the low-grade inflammatory response that, through the expression of inflammatory cytokines such as tumor necrosis factor (TNF)-␣ (1,2), will consequently determine insulin resistance leading ultimately to diabetes and macro-and microvascular diseases (1). TNF-␣ is the major negative regulator of the insulin receptor pathway and of adiponectin expression (3-5). TNF-␣ is regulated at a post-transcriptional level by TNF-␣ converting enzyme (TACE; also known as ADAM-17), a transmembrane sheddase/metalloprotease, which increases soluble TNF-␣ versus membrane TNF-␣ and therefore induces paracrine and systemic inflammation (6 -8).Tissue inhibitor of metalloproteinase (Timp)3 is able to block soluble TNF-␣ generation, therefore restraining the TNF system to the autocrine and juxtacrine activities exerted by membrane TNF-␣, which acts mainly through the p75 receptor and is less efficient than soluble TNF-␣ in inducing insulin resistance and atherosclerosis (6 -8). We have recently observed that a genetic transmission of Timp3 deficiency is able to impair glucose tolerance (9). Interestingly, Timp3 downregulation was found in adipose tissue of genetic mouse models of obesity, which may lead to the dysregulation of TACE/ADAM-17 activity (10). Therefore, we investigated the role of TACE in metabolic consequences of long-term, high-fat feeding. In this study, we show that Tace ϩ/Ϫ mice are in part protected by diet-induced o...

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“…2 The increased risk of cardiovascular disease in adults who are obese or overweight is well documented, 3,4 and similar findings have been reported from studies in adolescents. [5][6][7][8] Autonomic neuropathy is a common feature of both insulin-dependent and noninsulin-dependent diabetes. Small studies of symptomatic patients have shown that about 55% of diabetic patients with symptoms have demonstrable autonomic nervous system (ANS) dysfunction; the 5-year mortality rate in these series was 53% in those presenting with ANS dysfunction.…”

Section: Introductionmentioning

confidence: 99%

“…Concentrations of TNFa and soluble TNF-a receptors are higher in obese Japanese children than in nonobese Japanese children. 6 The concentration of soluble TNF-a receptors correlates positively with fasting plasma insulin and the homeostasis model assessment (HOMA) of insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Resting Heart Rate Variability, Inflammation, and Insulin Resistance in Overweight and Obese Adolescents

Parish

Todman

Jain

2016

Metabolic Syndrome and Related Disorders

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Background: The prevalence of obesity is increasing in young people in the United States. Lately, low-grade inflammation is recognized as accompanying obesity, a known risk factor for type 2 diabetes. Autonomic dysfunction is a prominent feature of adult diabetes, but its prevalence in adolescents in prediabetic states or with diabetes risk factors is unknown. We undertook to study obesity, inflammation, insulin resistance, and autonomic dysfunction together in a population of adolescents aged 13-18 years. Methods: Subjects gave a blood sample for cytokine analysis and a 5-min resting EKG for analysis of resting heart rate variability. TNF-a, IL-6, c-reactive protein (CRP), MCP-1, and IL-10 were analyzed by enzymelinked immunosorbent assay, and Fourier Transform was applied to electrocardiographic recordings of R-R intervals for analysis in frequency space. The HOMA calculation was used as an index of insulin sensitivity. Results: TNF-a, IL-6, CRP, MCP-1, HOMA, and insulin levels, but not serum glucose or IL-10, were higher in the obese subjects. Low-frequency (0.04-0.15 Hz) and high-frequency (0.15-0.4 Hz) fluctuations of R-R intervals were lower in the obese subjects, but the normalized low-frequency power was not different, suggesting proportional reduction in variability in both ranges and impairment of both sympathetic and parasympathetic systems. Conclusions: Chronic low-grade inflammation, insulin resistance, and autonomic dysfunction are present at an early age in obese youths; early detection of inflammation may facilitate meaningful lifestyle changes in this high-risk group.

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Serum tumor necrosis factor-α levels and components of the metabolic syndrome in obese adolescents

Cited by 112 publications

References 34 publications

A Prospective Study on the Prevalence of Metabolic Syndrome Among Healthy French Families

A Prospective Study on the Prevalence of Metabolic Syndrome Among Healthy French Families

Mice Heterozygous for Tumor Necrosis Factor-α Converting Enzyme Are Protected From Obesity-Induced Insulin Resistance and Diabetes

Resting Heart Rate Variability, Inflammation, and Insulin Resistance in Overweight and Obese Adolescents

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