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

It is recognized that the path from physical inactivity and obesity to lifestyle-related diseases involves low-grade inflammation, indicated by elevated plasma levels of inflammatory markers. Interestingly, contracting skeletal muscle is a major source of circulating interleukin-6 (IL-6) in response to acute exercise, but with a markedly lower response in trained subjects. As C-reactive protein (CRP) is induced by IL-6, we hypothesized that basal levels of IL-6 and CRP reflect the degree of regular physical activity when compared with other markers of inflammation associated with lifestyle-related morbidity. Fasting plasma/serum levels of IL-6, IL-18, CRP, tumur necrosis factor-alpha (TNF-alpha), soluble TNF receptor II (sTNF-RII), and adiponectin were measured in healthy non-diabetic men and women (n=84). The amount of leisure-time physical activity (LTPA) was assessed by interview. Obesity was associated with elevated insulin, C-peptide, triglycerides, low-density lipoprotein, IL-6, CRP, and adiponectin (all P<0.05). Importantly, physical inactivity was associated with elevated C-peptide (P=0.036), IL-6 (P=0.014), and CRP (P=0.007) independent of obesity, age, gender, and smoking. Furthermore, the LTPA score was inversely associated with IL-6 (P=0.017) and CRP (P=0.005), but with neither of the other markers. The results indicate that low levels of IL-6 and CRP - not IL-18, TNF-alpha, sTNF-RII, or adiponectin - reflect regular physical activity.
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PMID:Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity. 1707 27

Several autoimmune diseases are thought to be mediated in part by interleukin (IL)-18. Many are those with associated increased interferon-gamma (IFNgamma) levels such as systemic lupus erythematosus, macrophage activation syndrome, rheumatoid arthritis, Crohn's disease, psoriasis, and graft-versus-host disease. In addition, ischemia, including acute renal failure in human beings, appears to involve IL-18. Animal studies also support the concept that IL-18 is a key player in models of lupus erythematosus, atherosclerosis, graft-versus-host disease, and hepatitis. Unexpectedly, IL-18 plays a role in appetite control and the development of obesity. IL-18 is a member of the IL-1 family; IL-1beta and IL-18 are related closely, and both require the intracellular cysteine protease caspase-1 for biological activity. The IL-18 binding protein, a naturally occurring and specific inhibitor of IL-18, neutralizes IL-18 activities and has been shown to be safe in patients. Other options for reducing IL-18 activities are inhibitors of caspase-1, human monoclonal antibodies to IL-18, soluble IL-18 receptors, and anti-IL-18 receptor monoclonal antibodies.
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PMID:Interleukin-18 and the pathogenesis of inflammatory diseases. 1733 92

The neuroendocrine system affects the immune system through the neuroendocrine humoral outflow via the pituitary, and through direct neuronal influences via the sympathetic, parasympathetic (cholinergic) and peptidergic/sensory innervation of peripheral tissues. Circulating hormones or locally released neurotransmitters and neuropeptides regulate major immune functions, such as antigen presentation, antibody production, lymphocyte activity, proliferation and traffic, and the secretion of cytokines including the selection of T helper (Th)1 or Th2 cytokine responses. 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, substance P, ATP and the activation of the corticotropin-releasing hormone/substance P-histamine axis may actually facilitate inflammation, through induction of interleukin (IL)-1, IL-6, IL-8, IL-18, tumor necrosis factor (TNF)-alpha and CRP production. 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. Better understanding of the neuroendocrine control of inflammation may provide critical insights into mechanisms underlying a variety of common human immune-related diseases.
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PMID:Neurohormonal-cytokine interactions: implications for inflammation, common human diseases and well-being. 1771 84

In this study we measured serum concentrations of proinflammatory interleukin-6, interleukin-8, and interleukin-18 as well as anti-inflammatory interleukin-10 in 30 pregnant women with normal glucose tolerance, in 32 women with abnormal results of a 50-g glucose challenge test, and in 57 patients with gestational diabetes mellitus. Patients with gestational diabetes had significantly higher IL-6 (median 1.0 [0.7-1.5] vs. 0.7 [0.4-0.8] pg/ml, p=0.001), IL-8 (2.1 [1.1-4.2] pg/ml vs. 0.7 [0.4-0.9] pg/ml, p<0.0001), and IL-18 (249.3 [188.5-318.7] pg/ml vs. 186.7 [139.9-243.9] pg/ml, p=0.005) as well as lower IL-10 levels than healthy pregnant women (0.6 [0.5-1.5] pg/ml vs. 2.9 [1.8-3.2] pg/ml, p<0.0001). After adjusting for glucose, insulin, and BMI values, the differences in IL-8 and IL-18 became insignificant, whereas the differences in IL-6 and IL-10 levels remained highly significant (p<0.0001). The subjects with abnormal glucose challenge test results had higher IL-6 levels (0.9 [0.7-1.3] pg/ml, p=0.005) and similar levels of other cytokines as compared with the women with normal glucose tolerance. Our results suggest an impaired balance between circulating pro- and anti-inflammatory cytokines in patients with gestational diabetes; however, a significant contribution of maternal obesity to the increased levels of IL-8 and IL-18 should be underlined.
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PMID:Circulating pro- and anti-inflammatory cytokines in Polish women with gestational diabetes. 1844 86

Obesity is characterized by systemic low-grade inflammation in which adipose tissue, especially the omental depot, is thought to play a key role. We have previously shown that inflammation impairs 3T3-L1 preadipocyte cell line differentiation. To explore whether this interaction also takes place in vivo, the expression of several genes related to inflammation and adipocyte differentiation was assessed in human samples. Paired adipose tissue biopsies (from omental and subcutaneous depots) were obtained from 24 women: 6 lean normoglycemic and 18 obese volunteers with different glycemic states (normoglycemic, glucose-intolerant, or type 2 diabetic). The expression levels of CD14, IL-18, leptin, adiponectin, sterol regulatory element binding transcription factor 1 (SREBP1), peroxisome proliferator-activated receptor gamma (PPARgamma), pre-B-cell colony enhancing factor 1 (PBEF1) (or visfatin), glycerol-3-phosphate dehydrogenase 1 (soluble) (GPD1), lipoprotein lipase (LPL), fatty acid binding protein 4, adipocyte (FABP4), and hypoxia-inducible factor 1alpha were determined by quantitative real-time PCR. CD14 and IL-18 were overexpressed in omental adipose tissue compared with the subcutaneous depot, irrespective of the subject's obesity or diabetes status. A significant decrease of LPL, GPD1, and leptin expression was observed in omental tissue, and an inverse correlation between expression of CD14 and IL-18 and that of PPARgamma, LPL, and FABP4 was observed. The underexpression of omental lipogenic markers was more accentuated in the presence of glucose intolerance. Furthermore, adiponectin and SREBP1 expression was also significantly decreased in omental tissue of type 2 diabetic patients. PBEF1 and HIF1alpha expression remained comparable in all samples. Therefore, in humans, inflammation is increased in the omental depot, as evidenced by CD14 and IL-18 expression. In this localization, the inflammatory state is associated with a decreased expression of lipogenic markers, which is more pronounced in diabetic subjects.
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PMID:Inflammation is associated with a decrease of lipogenic factors in omental fat in women. 1883 93

Obesity is associated with increased severity of acute pancreatitis (AP). The cytokines IL-18 and IL-12 are elevated in patients with AP, and IL-18 levels are high in obesity. We aimed to develop a pathologically relevant model to study obesity-associated severe AP. Lean WT and obese leptin-deficient ob/ob mice received two injections of IL-12 plus IL-18. Survival, pancreatic inflammation, and biochemical markers of AP were measured. Dosing with IL-12 plus IL-18 induced 100% lethality in ob/ob mice; no lethality was observed in WT mice. Disruption of pancreatic exocrine tissue and acinar cell death as well as serum amylase and lipase levels were significantly higher in ob/ob than in WT mice. Edematous AP developed in WT mice, whereas obese ob/ob mice developed necrotizing AP. Adipose tissue necrosis and saponification were present in cytokine-injected ob/ob but not in WT mice. Severe hypocalcemia and elevated acute-phase response developed in ob/ob mice. The cytokine combination induced high levels of regenerating protein 1 and pancreatitis-associated protein expression in the pancreas of WT but not of ob/ob mice. To differentiate the contribution of obesity to that of leptin deficiency, mice received short- and long-term leptin replacement therapy. Short-term leptin reconstitution in the absence of major weight loss did not protect ob/ob mice, whereas leptin deficiency in the absence of obesity resulted in a significant reduction in the severity of the pancreatitis. In conclusion, we developed a pathologically relevant model of AP in which obesity per se is associated with increased severity.
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PMID:Interleukin-18, together with interleukin-12, induces severe acute pancreatitis in obese but not in nonobese leptin-deficient mice. 1851 22

Obesity is associated with infiltration of macrophages into adipose tissue. Adipose macrophages may contribute to an elevated inflammatory status by secreting a variety of proinflammatory mediators, including tumor necrosis factor alpha and interleukin-6 (IL-6). Recent data suggest that during diet-induced obesity the phenotype of adipose-resident macrophages changes from alternatively activated macrophages toward a more classical and pro-inflammatory phenotype. Here, we explore the effect of peroxisome proliferator-activated receptor gamma activation on obesity-induced inflammation in 129SV mice fed a high fat diet for 20 weeks. High fat feeding increased bodyweight gain, adipose tissue mass, and liver triglycerides. Rosiglitazone treatment further increased adipose mass, reduced liver triglycerides, and changed adipose tissue morphology toward smaller adipocytes. Surprisingly, rosiglitazone markedly increased the number of macrophages in adipose tissue, as shown by immunohistochemical analysis and quantification of macrophage marker genes CD68 and F4/80+. In adipose tissue, markers for classically activated macrophages including IL-18 were down-regulated, whereas markers characteristic for alternatively activated macrophages (arginase 1, IL-10) were up-regulated by rosiglitazone. Importantly, conditioned media from rosiglitazone-treated alternatively activated macrophages neutralized the inhibitory effect of macrophages on 3T3-L1 adipocyte differentiation, suggesting that alternatively activated macrophages may be involved in mediating the effects of rosiglitazone on adipose tissue morphology and mass. Our results suggest that short term rosiglitazone treatment increases infiltration of alternatively activated macrophages in adipose tissue. The alternatively activated macrophages might play a role in peroxisome proliferator-activated receptor gamma-dependent expansion and remodeling of adipose tissue.
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PMID:Peroxisome proliferator-activated receptor gamma activation promotes infiltration of alternatively activated macrophages into adipose tissue. 1854 27

Cardiovascular disease (CVD) remains the leading cause of morbidity and premature mortality in both women and men in most industrialized countries, and has for some time also established a prominent role in developing nations. In fact, obesity, diabetes mellitus and hypertension are now commonplace even in children and youths. Regular exercise is rapidly gaining widespread advocacy as a preventative measure in schools, medical circles and in the popular media. There is overwhelming evidence garnered from a number of sources, including epidemiological, prospective cohort and intervention studies, suggesting that CVD is largely a disease associated with physical inactivity. A rapidly advancing body of human and animal data confirms an important beneficial role for exercise in the prevention and treatment of CVD. In Part 1 of this review we discuss the impact of exercise on CVD, and we highlight the effects of exercise on (i) endothelial function by regulation of endothelial genes mediating oxidative metabolism, inflammation, apoptosis, cellular growth and proliferation, increased superoxide dismutase (SOD)-1, down-regulation of p67phox, changes in intracellular calcium level, increased vascular endothelial nitric oxide synthase (eNOS), expression and eNOS Ser-1177 phosphorylation; (ii) vascular smooth muscle function by either an increased affinity of the Ca2+ extrusion mechanism or an augmented Ca2+ buffering system by the superficial sarcoplasmic reticulum to increase Ca2+ sequestration, increase in K+ channel activity and/or expression, and increase in L-type Ca2+ current density; (iii) antioxidant systems by elevation of Mn-SOD, Cu/Zn-SOD and catalase, increases in glutathione peroxidase activity and activation of vascular nicotinamide adenine dinucleotide phosphate [(NAD(P)H] oxidase and p22phox expression; (iv) heat shock protein (HSP) expression by stimulating HSP70 expression in myocardium, skeletal muscle and even in human leucocytes, probably through heat shock transcription factor 1 activity; (v) inflammation by reducing serum inflammatory cytokines such as high-sensitivity C-reactive protein (hCRP), interleukin (IL)-6, IL-18 and tumour necrosis factor-alpha and by regulating Toll-like receptor 4 pathway. Exercise also alters vascular remodelling, which involves two forms of vessel growth including angiogenesis and arteriogenesis. Angiogenesis refers to the formation of new capillary networks. Arteriogenesis refers to the growth of pre-existent collateral arterioles leading to formation of large conductance arteries that are well capable to compensate for the loss of function of occluded arteries. Another aim of this review is to focus on exercise-related cardiovascular protection against CVD and associated risk factors such as aging, coronary heart disease, hypertension, heart failure, diabetes mellitus and peripheral arterial diseases mediated by vascular remodelling. Lastly, this review examines the benefits of exercise in mitigating pre-eclampsia during pregnancy by mechanisms that include improved blood flow, reduced blood pressure, enhanced placental growth and vascularity, increased activity of antioxidant enzymes, reduced oxidative stress and restored vascular endothelial dysfunction.
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PMID:Exercise, vascular wall and cardiovascular diseases: an update (Part 1). 1902 18

Obesity causes the specific upregulation of proinflammatory cytokines and chemokines. One of these cytokines, IL-18, has a well-known association with obesity. Our aim in this study was to test the effect of serum and intrafollicular IL-18 and IL-18 binding protein (BP) levels on in vitro fertilization outcomes in obese, overweight, and non-obese patients. Serum and pooled follicular fluid levels of IL-18, IL-18BP, and the IL-18/IL-18BP ratios were evaluated in 21 non-obese (body mass index [BMI] <25), 37 overweight (25<or=BMI<30), and 24 obese (BMI>or=30) patients undergoing in vitro fertilization. IL-18 and IL-18BP levels in serum and follicular fluid did not change with obesity. There was no correlation among serum intrafollicular IL-18, IL-18BP levels, and the number of oocytes retrieved and transferred, embryo grades or pregnancy ratios. The levels of serum and intrafollicular IL-18, IL-18BP, and the IL-18/IL-18BP ratios do not seem to be related to in vitro fertilization outcomes in obese, overweight, and non-obese patients.
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PMID:IL-18 and IL-18 binding protein concentrations in serum and ovarian follicular fluid do not affect in vitro fertilization outcomes in obese, overweight, and non-obese patients. 1909 47

Increasing adiposity predisposes to the development of the metabolic syndrome, in part, through adipose tissue dysregulation and inflammation. In addition, offspring nutrient-restricted (NR) in utero can exhibit an increased risk of early-onset insulin resistance and obesity, although the mechanisms remain unclear. We aimed to: 1) define adipose tissue ontogeny of key proinflammatory and endoplasmic reticulum stress gene expression from late fetal to early adult life and 2) examine the impact on these genes in gestational nutrient restriction. Pregnant sheep were fed 100% (control) or 50% (NR) of their nutritional requirements between early to mid (28-80 d, term approximately 147 d) or late (110-147 d) gestation. In control offspring, toll-like receptor 4 (TLR4), and the macrophage marker CD68, peaked at 30 d of life before declining. IL-18 peaked at 6 months of age, whereas the endoplasmic reticulum chaperone glucose-regulated protein 78 peaked at birth and subsequently declined through postnatal life. TLR4 and CD68 positively correlated with relative adipose tissue mass and with each other. Early to midgestational NR offspring had decreased abundance of IL-18 at 6 months of age. In late gestational NR offspring, CD68 was significantly lower at birth, a pattern that reversed in juvenile offspring, coupled with increased TLR4 abundance. In conclusion, the in utero nutritional environment can alter the adipose tissue inflammatory profile in offspring. This may contribute to the increased risk of insulin resistance or obesity, dependent on the timing of nutrient restriction. Establishing the optimal maternal diet during pregnancy could reduce the burden of later adult disease in the offspring.
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PMID:Adipose tissue inflammation: developmental ontogeny and consequences of gestational nutrient restriction in offspring. 1942 60


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