Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P43026 (lipopolysaccharide)
 62,215 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fever is considered an important host defense response but requires significant metabolic energy. During winter many animals must balance immune function with competing physiological demands (i.e. thermoregulation) to survive. Winterlike patterns of melatonin secretion induce a number of energy-saving adaptations. For instance, Siberian hamsters attenuate the duration of fever during simulated short winter day lengths, presumably to conserve energy. To determine the proximate role of melatonin in mediating this photoperiodic response, hamsters housed in long days were injected with saline or melatonin 4 h before lights off for either 1 or 6 wk and assessed for fever following injections of bacterial lipopolysaccharide. Fever duration was attenuated (32%) only in hamsters that decreased body mass, increased cortisol, and exhibited gonadal regression in response to 6 wk of melatonin. Because melatonin-treated hamsters lost significant body mass, fever was assessed in a second long-day group following ad libitum food intake, food restriction, or 24-h food deprivation. Food restriction sufficient to reduce body mass by approximately 25%, but not to reduce leptin, did not influence fever, and 24-h food deprivation virtually abolished fever. Our data suggest that long-term exposure to long-duration melatonin signals is required to induce the physiological changes necessary for short-day immune responses, perhaps involving interactions with hormones such as cortisol and leptin.
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PMID:Melatonin regulates energy balance and attenuates fever in Siberian hamsters. 1207 84

Peripheral administration of bacterial lipopolysaccharide (LPS) and various inflammatory cytokines to rodents is known to raise plasma levels of leptin, a potent satiety factor secreted from adipocytes, implying a role of leptin in endotoxin-induced anorexia. We previously reported no effect of LPS on serum leptin levels in sheep, despite marked anorexia and fever. Our results suggest that leptin might not be involved in the endotoxin-induced anorexia in ruminants. To test this idea, in the present study, plasma leptin levels were measured during acute experimental endotoxemia in Holstein cows. Intravenous injection of LPS induced anorexia accompanied with increases in plasma levels of cortisol and insulin, all of which are known to stimulate leptin secretion in rodent and human, while it did not affect plasma leptin levels at all in cows. Similar results were also obtained after injection of recombinant bovine tumor necrosis factor alpha. These results indicate that plasma leptin levels in cows during acute endotoxemia are differentially regulated from those in rodents, and that leptin might not be involved in the endotoxin-induced anorexia in ruminants.
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PMID:Plasma leptin responses to lipopolysaccharide and tumor necrosis factor alpha in cows. 1261 2

We examined the role of serotonin (5-HT) and the 5-HT(1A) and 5-HT(2C) receptors in the anorectic effects of centrally administered lipopolysaccharide (LPS), interleukin-1 beta (IL-1 beta), and leptin. Food intake was measured in rats after intracerebroventricular (ICV) injections of LPS (20 ng), IL-1 beta (10 ng), or leptin (1 microg) at lights out, followed by intraperitoneal (IP) injections of either the 5-HT(1A) autoreceptor agonist 8-hydroxy-2-(di-n-propylamino)tetraline (8-OH-DPAT) (125 microg/kg) or the 5-HT(2C) receptor antagonist SB 242084 (0.3 mg/kg) at the onset of anorexia. SB 242084 significantly attenuated the food intake reduction caused by all compounds (all P<.01). IP 8-OH-DPAT attenuated ICV IL-1 beta-induced anorexia (P<.01). We also tested the involvement of the median raphe 5-HT(1A) receptors in peripheral LPS- and IL-1 beta-induced anorexia. Rats were injected intraperitoneally with either LPS (100 microg/kg) or IL-1 beta (2 microg/kg) at lights out, and 8-OH-DPAT (4 nmol) was administered directly into the median raphe nucleus at the onset of anorexia. Median raphe injections of 8-OH-DPAT significantly attenuated both IL-1 beta- and LPS-induced anorexia (both P<.01). These results implicate the 5-HT(2C) receptors in the mediation of central LPS-, IL-1 beta-, and leptin-induced anorexia. Our results also suggest that the midbrain raphe nuclei play a role in mediating the anorectic response to peripheral LPS and IL-1 beta.
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PMID:Evidence for a role of the 5-HT2C receptor in central lipopolysaccharide-, interleukin-1 beta-, and leptin-induced anorexia. 1266 18

During an infection, a decrease in food intake together with elevated energy expenditure appears. Anorexia is one of the most common signs of illness and is often considered as an undesirable manifestation of sickness. However, compelling data demonstrate that anorexia constitutes an adaptative strategy systematically organised for pathogens elimination. Microbial products stimulate the production by immunocompetent cells of cytokines, which orchestrate the immune response. Since the administration of cytokines reduces food intake, it has been suggested that these agents play a key role in mediating anorexia during infection. This review details the mechanisms of cytokine-induced anorexia, focusing on the role of endogenously produced brain cytokines and more particularly interleukin-1 (IL-1). De novo synthesis of IL-1 occurs in the brain during peripheral infection mimicked by the administration of bacterial endotoxin lipopolysaccharide (LPS). Centrally produced IL-1 acts on its receptors to mediate anorexia as demonstrated by the use of knockout mice and specific IL-1 receptor antagonist. Functional neuroanatomy demonstrates further that LPS or IL-1 specifically activates the hypothalamic neurons that control food intake. Leptin is tightly regulated by IL-1, suggesting the involvement of this hormone in the anorexia of infection. The mechanisms by which hypothalamic arcuate nucleus neuropeptides, which are regulated by IL-1 and leptin, could mediate anorexia during infection are discussed.
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PMID:[Cytokines and nutritional disorders]. 1291 Jun 27

Ghrelin not only strongly stimulates GH secretion, but is also involved in energy homeostasis by stimulating food intake and promoting adiposity through a GH-independent mechanism. These effects of ghrelin may play an important role in the pathophysiology of inflammatory wasting syndrome, in which both the somatotropic axis and energy balance are altered. In this study we investigated plasma ghrelin concentrations after lipopolysaccharide (LPS) administration to rats, a model of the wasting syndrome and critical illness. In addition, the therapeutic potential of the antiwasting effects of ghrelin was explored using LPS-injected rats. A single LPS injection suppressed plasma ghrelin levels 6 and 12 h later. Maximal reduction was observed 12 h after LPS injection, in a dose-dependent manner. In contrast, plasma ghrelin levels were elevated after repeated LPS injections on d 2 and 5. Peripheral administration of ghrelin twice daily (10 nmol/rat) for 5 d increased body weight gain in repeated LPS-injected rats. Furthermore, both adipose tissue weight and plasma leptin concentrations were increased after ghrelin administration in these rats. In conclusion, plasma ghrelin levels are altered in LPS-injected rats, and ghrelin treatment may provide a new therapeutic approach to the wasting syndrome and critical illness.
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PMID:Alterations of plasma ghrelin levels in rats with lipopolysaccharide-induced wasting syndrome and effects of ghrelin treatment on the syndrome. 1296 78

Four multiparous lactating cows (175 to 220 d in milk [DIM]) were used in a 4 x 4 Latin square design to assess the effects of four doses (0.0, 0.5, 1.0, and 1.5 microg/kg of body weight) of lipopolysaccharide (LPS; Escherichia coli 0111:B4) on performance and plasma metabolite and hormone concentrations. In addition, effects of immune activation on in vitro hepatic metabolic capacity were evaluated in 12 multiparous lactating cows (150 to 220 DIM) infused with 0 (n = 6), 1.0 (n = 4) or 2.0 (n = 2) microg of LPS/kg. Milk production and DMI decreased linearly with LPS dose for 24 h after LPS infusion. Overall mean plasma tumor necrosis factor-alpha, insulin, glucagon, and cortisol concentrations increased linearly with LPS dose, and plasma beta-hydroxybutyrate decreased linearly by dose after LPS infusion. Infusion of LPS decreased the insulin:glucagon molar ratio, but did not affect plasma concentrations of growth hormone, insulin-like growth factor-1, leptin, or L-(+)-lactate. Plasma concentrations of glucose tended to increase initially and subsequently decrease, and there was a quadratic tendency for increased plasma nonesterified fatty acid concentrations after LPS administration. In vitro hepatic capacity for conversion of [1-(14)C]L-(+)-lactate and [1-(14)C]palmitate, but not [1-(14)C]propionate or [1-(14)C]L-alanine, to CO2 increased after LPS administration. Hepatic capacity to convert [1-(14)C]propionate to glucose tended to increase, but neither esterification nor the conversion of palmitate to acid soluble products was altered by LPS. The LPS infusion resulted in significant changes of endocrine mediators responsible for regulation of energy metabolism of lactating cows and tended to alter subsequent in vitro hepatic metabolic capacity.
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PMID:Effect of lipopolysaccharide on indices of peripheral and hepatic metabolism in lactating cows. 1467 74

It is not known why natural killer T (NKT) cells, which modulate liver injury by regulating local cytokine production, are reduced in leptin-deficient ob/ob mice. NKT cells express adrenoceptors. Thus, we hypothesize that the low norepinephrine (NE) activity of ob/ob mice promotes depletion of liver NKT cells, thereby sensitizing ob/ob livers to lipopolysaccharide (LPS) toxicity. To evaluate this hypothesis, hepatic NKT cells were quantified in wild-type mice before and after treatment with NE inhibitors, and in dopamine beta-hydroxylase knockout mice (which cannot synthesize NE) and ob/ob mice before and after 4 weeks of NE supplementation. Decreasing NE activity consistently reduces liver NKT cells, while increasing NE has the opposite effect. Analysis of hepatic and thymic NKT cells in mice of different ages demonstrate an age-related accumulation of hepatic NKT cells in normal mice, while liver NKT cells become depleted after birth in ob/ob mice, which have increased apoptosis of hepatic NKT cells. NE treatment inhibits apoptosis and restores hepatic NKT cells. In ob/ob mice with reduced hepatic NKT cells, hepatic T and NKT cells produce excessive T helper (Th)-1 proinflammatory cytokines and the liver is sensitized to LPS toxicity. NE treatment decreases Th-1 cytokines, increases production of Th-2 cytokines, and reduces hepatotoxicity. Studies of CD1d-deficient mice, which lack the receptor required for NKT cell development, demonstrate that they are also unusually sensitive to LPS hepatotoxicity. In conclusion, low NE activity increases hepatic NKT cell apoptosis and depletes liver NKT cells, promoting proinflammatory polarization of hepatic cytokine production that sensitizes the liver to LPS toxicity.
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PMID:Norepinephrine regulates hepatic innate immune system in leptin-deficient mice with nonalcoholic steatohepatitis. 1536 48

Anorexia and fever are important features of the host's response to inflammation that can be triggered by the bacterial endotoxin lipopolysaccharide (LPS) and the appetite suppressant leptin. Previous studies have demonstrated that LPS induces leptin synthesis and secretion in the periphery, and that the action of leptin on appetite suppression and fever are dependent on brain interleukin (IL)-1beta. However, the role of leptin as a neuroimmune mediator of LPS-induced inflammation has not been fully elucidated. To address this issue, we neutralized circulating leptin using a leptin antiserum (LAS) and determined how this neutralization affected LPS-induced anorexia, fever and hypothalamic IL-1beta. Adult male rats were separated into four treatment groups, namely LPS + normal sheep serum (NSS), LPS + LAS, saline + LAS and saline + NSS. Intraperitoneal injection of LPS (100 microg kg(-1)) induced a significant reduction in food intake and body weight, which were significantly reversed in the presence of LAS (1 ml kg(-1)), 8 and 24 h after treatment. In addition, LPS-induced fever was significantly attenuated by LAS over the duration of the fever response (8 h). Lipopolysaccharide induced an increase of circulating IL-6, another potential circulating pyrogen, which was not affected by neutralization of leptin at 2 h. Interleukin-1beta mRNA at 1 and 8 h, and IL-1 receptor antagonist (ra) at 2 h were significantly upregulated in the hypothalamus of LPS-treated animals. The induction of these cytokines was attenuated in the presence of LAS. These results are the first to demonstrate that leptin is a circulating mediator of LPS-induced anorexia and fever, probably through a hypothalamic IL-1beta-dependent mechanism.
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PMID:Circulating leptin mediates lipopolysaccharide-induced anorexia and fever in rats. 1538 82

Inflammation plays a major role in the development of chronic diseases such as cardiovascular disease and Type 2 diabetes. Further, it was demonstrated that obese animals and humans have significantly higher levels of circulating proinflammatory cytokines, such as interleukin-6 (IL-6). The aim of this study was to determine whether adipose tissue could be a major source of circulating IL-6 in leptin-deficient obese (ob/ob) mice by comparing the expression of IL-6 in different tissues of ob/ob mice. Our secondary goal was to determine whether preadipocytes are the source of adipose tissue IL-6. The ob/ob mice had higher levels of plasma IL-6 (P < 0.05) and adipose tissue IL-6 mRNA (P < 0.05) compared with lean mice. Interestingly, IL-6 mRNA levels of liver and spleen were not different between ob/ob and lean mice, whereas adipose tissue IL-6 mRNA levels were higher in the ob/ob mice compared with lean mice (P < 0.05). In addition, we showed that IL-6 secretion from the adipose tissue stromal vascular fraction cells was higher than that from fully differentiated adipocytes (P < 0.001). We further demonstrated that 3T3-L1 preadipocytes had significantly higher levels of lipopolysaccharide (LPS)-stimulated IL-6 mRNA and IL-6 secretion than differentiated 3T3-L1 adipocytes. Taken together, these data suggest that adipose tissue and preadipocytes from the adipose tissue stromal vascular fraction may contribute significantly to the increased plasma IL-6 levels in ob/ob mice.
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PMID:Expression of interleukin-6 is greater in preadipocytes than in adipocytes of 3T3-L1 cells and C57BL/6J and ob/ob mice. 1546 65

The aim of this study was to evaluate the impact of the lack of inducible NO synthase (iNOS) on body weight and adipose tissue mass as well as on plasma leptin and adiponectin in basal conditions and 6 h after lipopolysaccharide (LPS) administration in mice. Body weight was not different among male, six-week-old wild-type (WT) and iNOS-/- animals. However, the amount of epididymal white adipose tissue (EWAT) in iNOS-/- mice was significantly reduced (P<0.05). Circulating leptin and leptin mRNA in EWAT were decreased in iNOS-/- mice (P<0.05 and P<0.01, respectively). Plasma adiponectin and adiponectin mRNA were unchanged. LPS administration increased plasma leptin in both genotypes (P<0.05). Neither genotype nor treatment changed plasma adiponectin. In summary, iNOS-/- mice exhibited normal body weight but reduced adipose mass accompanied by hypoleptinemia. Leptin responsiveness to LPS in iNOS-/- mutants is preserved, showing that the LPS-induced rise in leptin is independent of the presence of functional iNOS. In addition, iNOS deficiency or LPS does not influence expression and circulating levels of adiponectin.
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PMID:Reduced adipose tissue mass and hypoleptinemia in iNOS deficient mice: effect of LPS on plasma leptin and adiponectin concentrations. 1555 8


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