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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although obesity-related fatty livers are vulnerable to damage from endotoxin, the mechanisms involved remain obscure. The purpose of this study was to determine if immunologic priming might be involved by determining if fatty livers resemble normal livers that have been sensitized to endotoxin damage by Propionibacterium acnes infection. The latter induces interleukin (IL)-12 and -18, causing a selective reduction of CD4+NK T cells, diminished IL-4 production, deficient production of T-helper type 2 (Th-2) cytokines (e.g., IL-10), and excessive production of Th-1 cytokines (e.g., interferon gamma [IFN-gamma]). Liver and spleen lymphocyte populations and hepatic cytokine production were compared in genetically obese, ob/ob mice (a model for obesity-related fatty liver) and lean mice. Obese mice have a selective reduction of hepatic CD4+NK T cells. Serum IL-18 is also increased basally, and the hepatic mRNA levels of IL-18 and -12 are greater after endotoxin challenge. Thus, up-regulation of IL-18 and IL-12 in fatty livers may reduce hepatic CD4+NK T cells. In addition, mononuclear cells from fatty livers have decreased expression of the adhesion molecule, leukocyte factor antigen-1 (LFA-1), which is necessary for the hepatic accumulation of CD4+NK T cells. Consistent with reduced numbers of hepatic CD4+NK T cells, mononuclear cells from fatty livers produce less IL-4. Furthermore, after endotoxin treatment, hepatic induction of IL-10 is inhibited, while that of IFN-gamma is enhanced. Thus, fatty livers have inherent immunologic alterations that may predispose them to damage from endotoxin and other insults that induce a proinflammatory cytokine response.
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PMID:Altered hepatic lymphocyte subpopulations in obesity-related murine fatty livers: potential mechanism for sensitization to liver damage. 1070 53

Obesity is associated with an increased risk of developing atherosclerosis, which may be mediated, at least in part, by increased secretion of proinflammatory cytokines by adipose tissue. We examined the hypothesis that circulating levels of IL-18 were elevated in obese women and would be reduced by weight loss. In a sample of 40 obese (body mass index, 36.4 +/- 3.1 kg/m(2)) women we found that plasma IL-18 levels were higher than in 40 normal weight control women (P < 0.01) and were positively associated with body weight (r = 0.46; P < 0.01) and visceral fat (waist to hip ratio; r = 0.39; P < 0.01). Caloric restriction-induced weight loss (> or = 10% of original weight) over 1 yr reduced IL-18 levels from 247 (204/309) to 147 (111/210) pg/ml (medians and 25%/75%; P < 0.01), positively associated with changes in body mass index and waist to hip ratio. In obese women, IL-18 levels are associated with body weight and abdominal fat deposition; weight loss is an important intervention to reduce IL-18 levels. IL-18 may be a novel cytokine operating in human obesity.
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PMID:Weight loss reduces interleukin-18 levels in obese women. 1216 23

Low-grade chronic inflammation is involved in the pathogenesis of the metabolic syndrome and atherosclerosis, and serum levels of inflammatory cytokines are useful cardiovascular risk markers. We have studied serum IL-18 concentrations in women with polycystic ovary syndrome (PCOS), focusing on its relationship with obesity and indexes of insulin resistance. Sixty consecutive women with PCOS and 34 healthy women were recruited. Serum levels of IL-18 and lipid and hormone profiles were measured. The insulin sensitivity index was calculated from glucose and insulin concentrations during an oral glucose tolerance test. Data were submitted to a multivariate general linear model introducing age as a covariate. Serum IL-18 levels were increased in PCOS patients compared with controls (P = 0.031) and in obese women compared with lean women (P = 0.018). No interaction between PCOS and obesity was found, suggesting that the influence of PCOS on serum IL-18 concentrations studied here was not different in lean women compared with obese women and that the influence of obesity on serum IL-18 concentrations was the same in the PCOS and control groups. Serum IL-18 levels correlated, after logarithmic transformation, with body mass index (r = 0.38; P < 0.0002), waist-to-hip ratio (r = 0.33; P < 0.001), and total testosterone levels (r = 0.24; P < 0.02), and inversely with the insulin sensitivity index (r = -0.23; P < 0.03). In conclusion, PCOS and obesity induce an increase in serum IL-18 levels, which are also associated with several indexes of global and visceral adiposity and with insulin resistance.
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PMID:Serum interleukin-18 concentrations are increased in the polycystic ovary syndrome: relationship to insulin resistance and to obesity. 1476 99

Liposuction is one of the more common elective surgical procedures in the US and is supposed to be on the increase. There are no reported studies specifically addressing the metabolic sequelae of liposuction in obesity. The aim of the present study was to investigate the role of large-volume liposuction on insulin resistance and circulating inflammatory markers in obese people. Thirty healthy premenopausal obese (body mass index (BMI) from 30 to 45) and 30 age-matched normal weight (BMI<25) women were studied. In obese women, insulin sensitivity, as measured by the Homeostasis Model Assessment (HOMA=fasting plasma glucose x fasting serum insulin divided by 25), as well as serum adiponectin, the novel adipocytokine with insulin sensitising properties, were significantly lower, as compared with nonobese women (p<0.01), indicating insulin resistance; on the contrary, serum concentrations of the proinflammatory cytokines IL-6, IL-18 and TNF-alpha, as well as the sensitive marker of inflammation C-reactive protein, were significantly higher (p<0.01). All obese women were submitted to a single large volume liposuction (superwet technique): the mean aspirate volume was 3540 ml (range 2550-4670), corresponding to a net lipid loss of 2.7+/-0.7 kg (mean+/-SD). After six months of stable body weight after liposuction, women were less insulin resistant (p<0.05), had reduced concentrations of IL-6, IL-18, TNF-alpha and CRP (p<0.05-0.02), and increased serum levels of adiponectin (p<0.02) and HDL-cholesterol (p<0.05). There was a significant correlation between the amount of fat aspirate and changes in HOMA (r=0.28, p<0.05), TNF-alpha (r=0.31, p<0.02), and adiponectin (r=-0.34, p<0.02), as well as between the decrease in TNF-alpha and the increase in adiponectin after the surgical procedure (r=-0.45, p<0.01). Our study demonstrates that liposuction is safe and free of metabolic sequelae in obese women, pending a careful screening of the patient. Moreover, it is associated with amelioration of insulin resistance and reduced circulating markers of vascular inflammation which may help obese subjects to reduce their cardiovascular risk.
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PMID:Effect of liposuction on insulin resistance and vascular inflammatory markers in obese women. 1592 45

Elevated plasma IL-18 is present in several conditions sharing insulin-resistance as common trait, but the association with insulin-resistance per se is not established. Plasma/serum IL-6, IL-18, TNF-alpha, soluble TNF receptor II (sTNFR2), and C-reactive protein (CRP) were measured in 97 patients with type 2 diabetes (DM) and 84 non-diabetic controls (CON). The association with insulin-resistance-estimated using the homeostasis model assessment (HOMA-IR)-was analyzed using multivariate linear and logistic regression. Compared to CON, DM demonstrated higher plasma levels of IL-18 (P = 0.001), IL-6 (P < 0.001), sTNFR2 (P = 0.005), and CRP (P < 0.001), while TNF-alpha was lower (P = 0.017). Plasma IL-18 increased across HOMA-IR quartiles in both DM and CON, both with and without adjustment for confounders (all P < 0.05). In contrast, neither IL-6, TNF-alpha, sTNFR2, nor CRP was associated with HOMA-IR in CON when adjusting for confounders. Accordingly, 50% increase of IL-18 corresponded to a marked increase of HOMA-IR in both DM and CON (DM: 26%, P = 0.014; CON: 25%, P = 0.003) after adjustment for confounders. Our results show that plasma IL-18 was associated with HOMA-IR independent of obesity and type 2 diabetes.
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PMID:Elevated plasma interleukin-18 is a marker of insulin-resistance in type 2 diabetic and non-diabetic humans. 1611 17

Cytokines mediate and control immune and inflammatory responses. Complex interactions exist between cytokines, inflammation and the adaptive responses in maintaining homeostasis, health, and well-being. Like the stress response, the inflammatory reaction is crucial for survival and is meant to be tailored to the stimulus and time. A full-fledged systemic inflammatory reaction results in stimulation of four major programs: the acute-phase reaction, the sickness syndrome, the pain program, and the stress response, mediated by the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. Common human diseases such as atopy/allergy, autoimmunity, chronic infections and sepsis are characterized by a dysregulation of the pro- versus anti-inflammatory and T helper (Th)1 versus Th2 cytokine balance. Recent evidence also indicates the involvement of pro-inflammatory cytokines in the pathogenesis of atherosclerosis and major depression, and conditions such as visceral-type obesity, metabolic syndrome and sleep disturbances. During inflammation, the activation of the stress system, through induction of a Th2 shift, protects the organism from systemic 'overshooting' with Th1/pro-inflammatory cytokines. Under certain conditions, however, stress hormones may actually facilitate inflammation through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor-alpha and C-reactive protein production and through activation of the corticotropin-releasing hormone/substance P-histamine axis. Thus, a dysfunctional neuroendocrine-immune interface associated with abnormalities of the 'systemic anti-inflammatory feedback' and/or 'hyperactivity' of the local pro-inflammatory factors may play a role in the pathogenesis of atopic/allergic and autoimmune diseases, obesity, depression, and atherosclerosis. These abnormalities and the failure of the adaptive systems to resolve inflammation affect the well-being of the individual, including behavioral parameters, quality of life and sleep, as well as indices of metabolic and cardiovascular health. These hypotheses require further investigation, but the answers should provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Cytokine dysregulation, inflammation and well-being. 1616 5

Insulin resistance and cardiovascular disease share common pathophysiological mechanisms, as the chronic activation of the innate immune system. This system constitutes the first line of body's defense and is constituted by different barriers (e.g., epithelia, adipose tissue) and different blood and tissue components (e.g., macrophages, neutrophils). This system generates the acute-phase response in which different acute-phase proteins and cytokines are produced in response to different aggressions as infections and traumatisms. The aim of this response is to eradicate these agents, to repair the harmed tissues, and, through increased insulin resistance, to optimize the energetic substrates, which will be drained to vital tissues and organs (i.e., brain and the immune system). Evolutionary pressures have led to survival of the fittest individuals, those with the genetics that allows the best defense against infection and periods of famine. Evidence is reported according to which gene polymorphisms in the molecules regulating the inflammatory cascade are associated with body composition, insulin action, and characteristics of the metabolic syndrome. The evolutive advantages of increased inflammatory responses, hypersecretion of proinflammatory cytokines [tumor necrosis factor-alpha (TNF-alpha), interleukin (IL)-1beta, IL-6, and IL-18], or decreased anti-inflammatory molecules (adiponectin, certain TNF-alpha isoforms, soluble CD14, etc.), would lead in westernized countries to chronic inflammation conditions, such as obesity and type 2 diabetes, resulting in cardiovascular disease.
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PMID:Genetic predispositions to low-grade inflammation and type 2 diabetes. 1647 51

Here we report the presence of hyperphagia, obesity and insulin resistance in knockout mice deficient in IL-18 or IL-18 receptor, and in mice transgenic for expression of IL-18 binding protein. Obesity of Il18-/- mice resulted from accumulation of fat tissue based on increased food intake. Il18-/- mice also had hyperinsulinemia, consistent with insulin resistance and hyperglycemia. Insulin resistance was secondary to obesity induced by increased food intake and occurred at the liver level as well as at the muscle and fat-tissue level. The molecular mechanisms responsible for the hepatic insulin resistance in the Il18-/- mice involved an enhanced expression of genes associated with gluconeogenesis in the liver of Il18-/- mice, resulting from defective phosphorylation of STAT3. Recombinant IL-18 (rIL-18) administered intracerebrally inhibited food intake. In addition, rIL-18 reversed hyperglycemia in Il18-/- mice through activation of STAT3 phosphorylation. These findings indicate a new role of IL-18 in the homeostasis of energy intake and insulin sensitivity.
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PMID:Deficiency of interleukin-18 in mice leads to hyperphagia, obesity and insulin resistance. 1673 81

Overproduction of proinflammatory factors is associated with obesity and diabetes. Interleukin (IL)-18 as a member of IL-1 cytokine family is increased in obese, in diabetic, and even in polycystic ovary syndrome (PCOS) patients. In the present study we evaluated the association of serum IL-18 levels with insulin resistance in PCOS women. Forty-two PCOS women and 38 control subjects were enrolled in this study and matched with respect to age and body mass index (BMI). Serum IL-18 levels and hormones were measured for all subjects. Furthermore, euglycemic hyperinsulinemic clamp test was performed in selected 30 PCOS women and 11 control subjects. Serum IL-18 levels were elevated in PCOS women compared with the control (p = 0.033). IL-18 levels were positively correlated with homeostasis model assessment index (HOMA) beta index, which assesses beta cell function (p = 0.035), but were inversely correlated with clamp indices, which best represent insulin resistance status: M, Clamp ISI*100, and MCRg values (p = 0.006, 0.010, and 0.009 respectively). No correlation was found between IL-18 and age, BMI, waist-to-hip ratio (WHR), lipid profile, dehydroepiandrosterone-sulfate (DHEAS), sex hormone- binding globulin (SHBG), or fasting insulin levels. In conclusion, in the present study, serum IL-18 levels were significantly increased in PCOS women and firmly associated with insulin resistance displayed by euglycemic hyperinsulinemic clamp test. It indicates that IL-18 may be a contributing factor linking inflammation and insulin resistance in PCOS women.
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PMID:Elevated serum levels of interleukin-18 are associated with insulin resistance in women with polycystic ovary syndrome. 1694 80

Interleukin (IL)-18 is a proinflammatory cytokine that plays an important role in both innate and adaptive immune responses against viruses and intracellular pathogens. Increased levels of circulating IL-18 from HIV-1 infected patients have been reported especially in the advanced and late stages of the disease, whereas in the initial stage serum levels of IL-18 were not increased. In contrast, low production of Il-18 was observed in vitro from peripheral blood mononuclear cells (PBMC) of HIV-1 infected patients, and these results were also observed in macaques infected with simian immunodeficiency virus (SIV). In addition, decreased IL-18 production from PBMC was significantly correlated with low production of IL-2. Furthermore, serum levels of IL-18 significantly decreased after highly active antiretroviral therapy. During the early stage of HIV-1 infection there is a decreased production of gamma interferon (IFN), IL-12 and IL-2 as well as not activation of IL-18 production and this leads to inhibition of Th1 immune response, whereas in the advanced stage of the disease, strong activation of IL-18 production along with persistent decreased production of gamma IFN, IL-12 and IL-2 may promote a Th2 immune response, which leads to persistent viral replication. Several studies have shown increased levels of IL-18 in HIV-seronegative subjects with obesity, insulin resistance and type II diabetes. Metabolic disorders, fat redistribution and cardiovascular manifestations are becoming more frequent in HIV-1 infected patients treated with antiretroviral drugs. Consequently, involvement of IL-18 in these disorders has been postulated and demonstrated in patients with lipodistrophy, or with hypertriglyceridemia. Finally, higher serum levels of IL-18 may represent an useful marker in HIV-1 infected patients with metabolic disorders and fat redistribution, as well as a sensitive predictor of cardiovascular complications in treated patients.
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PMID:Interleukin-18: a proinflammatory cytokine in HIV-1 infection. 1707 17


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