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

Cytokine-induced sickness behavior was recognized within a few years of the cloning and expression of interferon-alpha, IL-1 and IL-2, which occurred around the time that the first issue of Brain, Behavior, and Immunity was published in 1987. Phase I clinical trials established that injection of recombinant cytokines into cancer patients led to a variety of psychological disturbances. It was subsequently shown that physiological concentrations of proinflammatory cytokines that occur after infection act in the brain to induce common symptoms of sickness, such as loss of appetite, sleepiness, withdrawal from normal social activities, fever, aching joints and fatigue. This syndrome was defined as sickness behavior and is now recognized to be part of a motivational system that reorganizes the organism's priorities to facilitate recovery from the infection. Cytokines convey to the brain that an infection has occurred in the periphery, and this action of cytokines can occur via the traditional endocrine route via the blood or by direct neural transmission via the afferent vagus nerve. The finding that sickness behavior occurs in all mammals and birds indicates that communication between the immune system and brain has been evolutionarily conserved and forms an important physiological adaptive response that favors survival of the organism during infections. The fact that cytokines act in the brain to induce physiological adaptations that promote survival has led to the hypothesis that inappropriate, prolonged activation of the innate immune system may be involved in a number of pathological disturbances in the brain, ranging from Alzheimer's disease to stroke. Conversely, the newly-defined role of cytokines in a wide variety of systemic co-morbid conditions, ranging from chronic heart failure to obesity, may begin to explain changes in the mental state of these subjects. Indeed, the newest findings of cytokine actions in the brain offer some of the first clues about the pathophysiology of certain mental health disorders, including depression. The time is ripe to begin to move these fundamental discoveries in mice to man and some of the pharmacological tools are already available to antagonize the detrimental actions of cytokines.
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PMID:Twenty years of research on cytokine-induced sickness behavior. 1708 43

Resistin is a 12.5-kDa cysteine-rich protein secreted from adipose tissue and is an important factor linking obesity with insulin resistance. Here, we investigated the effect of resistin on glucose tolerance in adult human hepatocytes (L-02 cells). In this study, resistin cDNA was transfected into L-02 cells, and glucose concentration and glucokinase activity were determined subsequently. The data indicated resistin impaired, insulin-stimulated glucose utilization, which implied liver was a target tissue of resistin. To understand its molecular mechanism, mRNA levels of key genes in glucose metabolism and insulin signaling pathway were analyzed. The results demonstrated resistin-stimulated expression of glucose-6-phosphatase (G6Pase), sterol regulatory element-binding protein 1c (SREBP1c) and suppressor of cytokine signaling 3 (SOCS-3), repressed expression of peroxisome proliferator-activated receptor gamma (PPARgamma) as well as insulin receptor substrate 2 (IRS-2). Given that glucokinase (GK) activity and glucose transporter 2 (GLUT2) expression were not altered, we presumed that resistin did not effect them. Moreover, resistin lowered mRNA levels of IRS-2 while stimulating SOCS-3 expression, which suggests it impairs glucose tolerance by blocking the insulin signal transduction pathway.
Eur Cytokine Netw 2006 Sep
PMID:Resistin overexpression impaired glucose tolerance in hepatocytes. 1719 39

Interest in the biology of white adipose tissue (WAT) has increased dramatically since the discovery of leptin in 1994. The identification of the product of the gene obese (ob) threw light on the role of adipose tissue in the physiopathology of obesity-related diseases, and spurred the identification of numerous other adipokines, many of a pro-inflammatory nature. It has become increasingly evident that WAT-derived cytokines mediate between obesity-related exogenous factors (nutrition and lifestyle) and the molecular events that lead to metabolic syndrome and inflammatory and/or autoimmune conditions. Here, we review recent adipokine research, with particular attention to the roles of leptin, adiponectin, resistin, visfatin, apelin, vaspin and hepcidin in such conditions.
Cytokine Growth Factor Rev
PMID:The emerging role of adipokines as mediators of inflammation and immune responses. 1750 80

White adipose tissue (WAT) is a major source of production of cytokines involved in chronic diseases such as obesity, type 2 diabetes, and atherosclerosis. Long-term exercise has been proposed as a therapy to reduce chronic inflammation. We investigated here the influence of an intense exercise training (over 7 weeks) on several cytokine concentrations including interleukin 1 receptor antagonist (IL-1ra), IL-1beta, and IL-12 in serum, WAT, and skeletal muscle (SM) from non-obese rats. Two groups of 10 rats were investigated: one group was progressively trained (the two last weeks: 120min per day, 25m/min, 7% grade, 5 days per week) and the other age-matched group was used as a sedentary control. Compared to sedentary rats, weight gain was lower in the trained rats (P<0.01). In WAT, concentrations of IL-1ra, IL-1beta, and IL-12 were lower (P<0.001 for IL-1ra and IL-12, P<0.05 for IL-1beta) while they were higher in SM (P<0.01 for IL-1ra, P<0.001 for IL-1beta, P<0.05 for IL-12), and similar in serum. Significant correlations were noted between (i) body weight and WAT concentrations of IL-1ra, IL-1beta, and IL-12 (0.595, 0.450, and 0.481, respectively), (ii) body weight and IL-1beta concentration in SM (-0.526). We also observed significant negative correlations between WAT and SM concentrations of the three cytokines. We show here for the first time that intense exercise training with weight loss reduced concentrations of IL-1ra, IL-1beta, and IL-12 in WAT, while it increased them in SM. These results suggest that exercise could help reduce inflammation in WAT through mobilization of immune cells producing pro- and anti-inflammatory cytokines in SM.
Cytokine 2007 Oct
PMID:Effects of chronic exercise on cytokine production in white adipose tissue and skeletal muscle of rats. 1782 74

Thyroid hormones act on several aspects of metabolic and energy homeostasis influencing body weight, thermogenesis, and lipolysis in adipose tissue. Adipocytokines are biologically active substances produced by adipocyte with different physiological functions. These substances have multiple effects on several tissues acting on the intermediate and energy metabolism. For these reasons, attention has recently been focused on the possible relationship between adipocytokines, thyroid status, and thyroid dysfunction. Leptin, a signal of satiety to the brain and regulator of insulin and glucose metabolism, reflects the amount of fat storage and is considered as a pro-inflammatory adipocytokine. Adiponectin is inversely related to the degree of adiposity, increases insulin sensitivity, and may have antiatherogenic and anti-inflammatory properties. Resistin impairs glucose homeostasis and insulin action in mice but not in humans. Resistin might be considered a pro-inflammatory adipocytokine and participate in obesity-associated inflammation. Several reports indicate that leptin regulates thyroid function at hypothalamic-hypophyseal level and, conversely, thyroid hormones might control leptin metabolism at least in some animals studies. Both adiponectin and thyroid hormones share some physiological actions as reduction of body fat by increasing thermogenesis and lipid oxidation. Resistin also seems to be regulated by thyroid hormones, at least in rats. Thyroid dysfunction does not significantly affect serum leptin concentrations. Serum levels of adiponectin are no influenced by thyroid hypofunction; however, hyperthyroidism is associated with normal or elevated adiponectin levels. Finally, discordant results in resistin levels in thyroid dysfunction have been reported in humans.
Cytokine 2007 Nov
PMID:Influence of thyroid dysfunction on serum concentrations of adipocytokines. 1800 29

Adipose tissue-derived cytokines are presumably involved in obesity-associated pathologies including type 2 diabetes and atherosclerosis. Here we studied the lipopolysaccharide (LPS)-induced expression dynamics of tumor necrosis factor-alpha (TNFalpha), interleukin-6 (IL-6), IL-8 and IL-10 in human adipose tissue biopsies, in preadipocyte-derived adipocytes, and in mesenchymal stem cell (MSC)-derived adipocytes. TNFalpha, IL-6, IL-8 and IL-10 secretions by adipose tissue explants were increased 5.5-, 19.5-, 3.5- and 12.5-fold, respectively, by LPS (1 microg/mL) administration. Concordantly, IL-6 and IL-8 release was dose-dependently induced in MSC-derived adipocytes by LPS (>10 pg/mL). In contrast, TNFalpha and IL-10 remained undetectable even at the highest LPS dose (1 microg/mL) after 24h. In MSC- and preadipocyte-derived adipocytes, respectively, exposure to LPS evoked a weak and transient induction of TNFalpha mRNA whereas induction of IL-6 and IL-8 mRNA were pronounced and sustained for at least 24h. Basal glucose uptake, lipolysis and IL-6 mRNA were induced by exogenous TNFalpha (10 ng/mL) but not by IL-6 (10 ng/mL), IL-8 (100 ng/mL) and IL-10 (20 ng/mL). In this adipocyte model TNFalpha induces well known metabolic effects, but together with previous reports these data suggest that inflammation-induced TNFalpha may derive from non-adipocyte sources in adipose tissue, likely to be macrophages.
Cytokine 2008 Jan
PMID:LPS induces interleukin-6 and interleukin-8 but not tumor necrosis factor-alpha in human adipocytes. 1806 Aug 2

Tumour necrosis factor alpha (TNFalpha) induces platelet-activating factor (PAF) synthesis in many inflammatory cells. Here, we investigate the possibility that TNFalpha stimulates PAF synthesis in rat adipocytes and preadipocytes and that phosphoinositide 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) are implicated in this process. Primary cultures were incubated with [3H]lyso-PAF and stimulated by TNFalpha in the presence or absence of wortmannin. We found that, although both cultures synthesized PAF at a similar basal rate, TNFalpha-induced PAF synthesis in adipocytes was 7-fold higher than in preadipocytes. This suggested a maturation of PAF-TNFalpha interrelationship during adipocyte differentiation. Wortmannin enhanced TNFalpha-dependent PAF synthesis in adipocytes but not in preadipocytes, indicating the negative control by PI3K in mature cells. PAF increase was due to the regulation of its biosynthesis since PAF-acetylhydrolase (PAF-AH) activity was TNFalpha- and wortmannin-independent. Our hypothesis is that PAF mediates TNFalpha inflammatory effects in both adipocytes and preadipocytes and that this pathway is enhanced during adipocyte differentiation, a mechanism which is highly active during the development of obesity.
Cytokine 2008 Feb
PMID:TNFalpha is a potent inducer of platelet-activating factor synthesis in adipocytes but not in preadipocytes. Differential regulation by PI3K. 1818 Jan 65

Adipose-derived cytokines play a prominent role in mediating the metabolic consequences of obesity and excess body fat. Given this, we hypothesized that alterations in adipose tissue stores incurred with exercise training would be reflected in changes in systemic cytokine concentrations. The Studies of Targeted Risk Reduction Intervention through Defined Exercise, where pronounced changes in adipose tissue stores were observed in the absence of significant changes in dietary intake, provided an ideal setting in which to test this hypothesis. Participants were randomized to 6 months of inactivity or one of 3 types of aerobic exercise training regimens: low-amount-moderate-intensity, low-amount-vigorous-intensity, and high-amount-vigorous-intensity. Plasma samples were collected at baseline and 2 weeks after cessation of 6 months of exercise training or inactivity. In 189 participants, concentrations of 17 cytokines were measured using Bio-Plex Cytokine Assays (Bio-Rad, Hercules, CA); 10 additional cytokines were measured in 60 of these subjects. Of all cytokines tested, the only concentration changes that approached statistical significance were those for granulocyte monocyte-colony stimulating factor and vascular endothelial growth factor, which appeared to increase with training in the low-amount-high-intensity group only (P < .05 for both cytokines). No response to exercise training was noted for any additional cytokine in any of the groups. No relationships were observed between changes in cytokine concentrations and changes in fat mass or other measures of body habitus. In contradiction to our hypothesis, despite significant alterations in body composition, exercise training produced limited cytokine responses.
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PMID:Relationships between adipose tissue and cytokine responses to a randomized controlled exercise training intervention. 1832 63

Obesity is associated with asthma and airway hyperresponsiveness. Leptin modulates some of the proinflammatory effects observed in obesity. The objective of this study was to determine the effects of leptin on airway smooth muscle responses. The effect of leptin (0.1-100 ng/ml) on migration (toward platelet-derived growth factor [PDGF], 10 ng/ml, across collagen-coated membrane in Transwell culture plates), proliferation (by BrDU incorporation), and cytokine production (by Bioplex bead assay) of cultured human airway smooth muscle cells from nine nonasthmatic donors was assessed. Effects of leptin on the contractile responses were studied in bovine tracheal smooth muscle rings. Leptin receptor expression and activation of STAT-3, Src kinase, Suppressor of Cytokine Signaling-3 (SOCS-3), and COX were evaluated by Western blotting and PCR. PGE(2) levels in supernatant were assessed by enzyme immunoassay. Human airway smooth muscle cells express leptin receptor, which, when engaged, phosphorylated STAT-3. Leptin inhibited PDGF-induced human airway smooth muscle migration and proliferation and IL-13-induced eotaxin production. Leptin did not stimulate cytokine synthesis and did not evoke contractile responses or inhibit isoproterenol-induced relaxation of carbachol-induced contraction of bovine tracheal rings. The inhibitory effects on migration and eotaxin production are not due to activation of SOCS-3 but are partly due to increased production of PGE(2) because they were attenuated by indomethacin. In conclusion, leptin inhibited human airway smooth muscle proliferation, migration toward PDGF, and IL-13-induced eotaxin production. This is partly mediated by PGE(2) secretion from smooth muscle cells induced by leptin. The association between obesity and asthma is unlikely to be due to a direct effect of leptin on airway smooth muscle.
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PMID:The effects of leptin on airway smooth muscle responses. 1842 Oct 18

Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS.
Cytokine 2008 Oct
PMID:Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines. 1872 87


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