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)

Interleukins (IL) are key mediators of the host response to infection and inflammation. Leptin is secreted by adipose tissue and plays an important role in the control of food intake. Administration of lipopolysaccharide (LPS), tumor necrosis factor (TNF), or IL-1 acutely increases leptin mRNA and protein levels. To investigate the role of IL-1 beta and IL-6 in leptin expression during inflammation, we used IL-1 beta-deficient (-/-) and IL-6 -/- mice. Mice were injected intraperitoneally with LPS or subcutaneously with turpentine, as models of systemic or local inflammation, respectively. In IL-1 beta +/+ mice, both LPS and turpentine increased leptin mRNA and circulating leptin. In contrast, neither LPS nor turpentine increased leptin levels in IL-1 beta -/- mice. In IL-6 +/+ or IL-6 -/- mice, turpentine increased leptin protein to comparable levels. We conclude that IL-1 beta is essential for leptin induction by both LPS and turpentine in mice, but IL-6 is not.
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PMID:IL-1 beta mediates leptin induction during inflammation. 945 19

Leptin is induced by lipopolysaccharide (LPS) and cytokines. We investigated the role of leptin in LPS-induced toxicity using leptin-deficient (ob/ob) and leptin receptor-deficient (db/db) mice. Sensitivity to LPS-induced mortality is significantly greater in ob/ob mice compared with their own lean littermates but not in db/db mice. LPS reduced serum glucose in both ob/ob and db/db mice but induced corticosterone only in db/db mice. Despite the very high basal levels of serum leptin in db/db mice, a twofold increase in serum leptin levels was observed after LPS in both db/db mice and their lean littermates. No differences were detected in LPS-induced serum levels of interleukin (IL)-1beta, tumor necrosis factor, macrophage inflammatory protein-1alpha, and interferon-gamma in ob/ob mice compared with their own littermates. In contrast, a blunted induction of IL-10 and IL-1 receptor antagonist (IL-1Ra) was observed in ob/ob mice compared with their littermates. In vitro, leptin induced IL-1Ra production and upregulated the IL-1Ra induction by LPS in macrophages. Moreover, treatment with leptin reversed the increased sensitivity to LPS-induced lethality found in ob/ob mice. These results suggest that leptin participates in the host response to inflammation by modulating the host immune and cytokine responses after LPS.
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PMID:Leptin deficiency enhances sensitivity to endotoxin-induced lethality. 988 87

Leptin regulates adiposity by reducing caloric intake and increasing energy expenditure. Because loss of body weight is common during infectious, neoplastic, and autoimmune diseases of the central nervous system, we examined whether an injection of lipopolysaccharide (LPS) into the lateral cerebral ventricle increases circulating leptin levels in fasted mice. Centrally injected LPS (100 ng) induced a two-fold elevation in plasma leptin 6, 12, and 18 h post-injection. Peripheral injection of the same dose of LPS did not affect leptin secretion. This suggests that inflammatory stimuli localized in the CNS are sufficient to induce leptin secretion in the periphery. The induction of leptin by inflammatory stimuli in the brain may be part of a feed-back loop that contributes to anorexia and cachexia in many CNS-oriented diseases.
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PMID:Intracerebroventricular injection of lipopolysaccharide increases plasma leptin levels. 1009 53

The Ob gene product, leptin, is an adipocyte-secreted hormone that centrally regulates weight control. However, leptin receptor is expressed not only in the central nervous system, but also in other systems such as reproductive and hematopoietic tissues. Human leptin has previously been shown to enhance cytokine production by murine peritoneal macrophages. In this paper we show that human leptin stimulates proliferation in a dose-dependent manner and functionally activates human circulating monocytes in vitro, by inducing the production of cytokines such as TNF-alpha and IL-6. Proliferation was assessed both by [3H]thymidine and bromodeoxyuridine incorporation at 48 h. We also checked the leptin stimulated monocyte expression of activation markers by flow cytometry: CD25, HLA-DR, CD38, CD71, CD11b, and CD11c expression increased after 72 h. Moreover, leptin increases the expression of the early activation marker CD69 in monocytes but not in lymphocytes. The stimulation produced by leptin is comparable to that produced by endotoxin [lipopolysaccharide (LPS)]. In addition, leptin can potentiate the stimulatory effect of LPS or PMA. Furthermore, we studied cytokine production (TNF-alpha and IL-6) simultaneously by flow cytometric detection of intracellular cytokines in the activated monocytes. Leptin produced a dose-dependent increase in the number of activated monocytes producing cytokines. These data indicate that leptin is a potent stimulatory hormone on human peripheral blood monocytes and suggest that it may have a role as a proinflammatory cytokine.
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PMID:Human leptin stimulates proliferation and activation of human circulating monocytes. 1035 75

Leptin has been implicated in the regulation of anorexia associated with cachexia in rodents and humans. Regulation of leptin expression is under complex endocrine and metabolic control. To determine if leptin expression is regulated by acute inflammation and to define the endocrine and metabolic factor(s) that regulates leptin expression during acute inflammation, castrate male pigs (ad libitum fed, used as their own controls) were treated with saline (control period) and endotoxin (lipopolysaccharide [LPS] period). Frequent blood samples were collected to identify dynamic changes in hormones and metabolites that are known to regulate leptin expression. LPS caused fever and elevated plasma cortisol (p < 0.0004), tumor necrosis factor-alpha (TNF-alpha) (p < 0.0001), and plasma nonesterified fatty acids (NEFA) (p < 0.001) compared with control. Circulating insulin (p < 0.01), glucose (p < 0.003), and insulin-like growth factor-1 (IGF-1) (p < 0.0001), as well as adipose leptin mRNA abundance (p < 0.01), were profoundly reduced following LPS treatment compared with control. Our data indicate that during acute endotoxemia (1-10 h after injection), leptin gene expression is decreased compared with ad libitum fed animals and is more closely related to energy homeostasis than cytokine profiles in plasma.
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PMID:Leptin expression is reduced with acute endotoxemia in the pig: correlation with glucose, insulin, and insulin-like growth factor-1 (IGF-1). 1067 Jun 56

Malnutrition compromises immune function, reducing resistance to infection. We examine whether the decrease in leptin induced by starvation increases susceptibility to lipopolysaccharide (LPS)- and tumor necrosis factor (TNF)-induced lethality. In mice, fasting for 48 hours enhances sensitivity to LPS. Decreasing the fasting-induced fall in leptin by leptin administration markedly reduced sensitivity to LPS. Although fasting decreases basal leptin levels, LPS treatment increased leptin to the same extent as in fed animals. Fasting increased basal serum corticosterone; leptin treatment blunted this increase. Fasting decreased the ability of LPS to increase corticosterone; leptin restored the corticosterone response to LPS. Serum glucose levels were decreased in fasted mice and LPS induced a further decrease. Leptin treatment affected neither basal glucose nor that after LPS. LPS induced a fivefold greater increase in serum TNF in fasted mice, which was blunted by leptin replacement. In contrast, LPS induced lower levels of interferon-gamma and no differences in interleukin-1beta in fasted compared to fed animals; leptin had no effect on those cytokines. Furthermore, fasting increased sensitivity to the lethal effect of TNF itself, which was also reversed by leptin treatment. Thus, leptin seems to be protective by both inhibiting TNF induction by LPS and by reducing TNF toxicity.
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PMID:Reduced leptin levels in starvation increase susceptibility to endotoxic shock. 1079 89

Leptin, the product of the ob gene, regulates food intake, energy expenditure, and other physiological functions of the peripheral tissues. Leptin receptors have been identified in the hypothalamus and in extrahypothalamic tissues. Increased circulating leptin levels have been correlated with cardiovascular disease, obesity, aging, infection with bacterial lipopolysaccharide, and high-fat diets. All these conditions have also been correlated with increased vascular calcification, a hallmark of atherosclerotic and age-related vascular disease. In addition, the differentiation of marrow osteoprogenitor cells is regulated by leptin. Thus, we hypothesized that leptin may regulate the calcification of vascular cells. In this report, we tested the effects of leptin on a previously characterized subpopulation of vascular cells that undergo osteoblastic differentiation and calcification in vitro. When treated with leptin, these calcifying vascular cells had a significant 5- to 10-fold increase in alkaline phosphatase activity, a marker of osteogenic differentiation of osteoblastic cells. Prolonged treatment with leptin enhanced the calcification of these cells, further supporting the pro-osteogenic differentiation effects of leptin. Furthermore, the presence of the leptin receptor on calcifying vascular cells was demonstrated using reverse transcriptase polymerase chain reaction, immunocytochemistry, and Western blot analysis. We also identified the presence of leptin receptor in the mouse artery wall, localized to subpopulations of medial and adventitial cells, and the expression of leptin by artery wall cells and atherosclerotic lesions in mice. Taken together, these results suggest that leptin regulates the osteoblastic differentiation and calcification of vascular cells and that the artery wall may be an important peripheral tissue target of leptin action.
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PMID:Leptin enhances the calcification of vascular cells: artery wall as a target of leptin. 1134 6

Bacterial lipopolysaccharide (LPS) stimulates massive release of tumor necrosis factor-alpha (TNF-alpha) together with nitric oxide (NO) and a lessor release of leptin. We hypothesized that other types of stress such as that of surgery might also release these cytokines and NO. Adult male rats were anesthetized with ketamine/acepromazine/xylazine anesthesia (90 + 2 + 6 mg/ml, respectively) and an external jugular catheter was inserted for removal of blood samples (0.6 ml) at various times postoperatively. Plasma TNF-alpha was almost undetectable in decapitated rats and was near zero immediately following the placement of the jugular catheter (time zero [t0]). As the rats awakened from anesthesia, there was a rise in TNF-alpha at 30 min that peaked at 2 hr with a 400-fold increase and then precipitously declined 40-fold to a level still greater than zero at 3 hr. At 6 hr on the following morning, TNF-alpha values were near zero, but following connection of tubing and withdrawal of the initial blood sample, there was a 100-fold increase 1 hr later, followed by a decline over the next 3 hr. In contrast, plasma [NO/NO2] from decapitated rats was 117 microM. Values at tO were decreased and plummeted 4-fold within 30 min, then rose slightly in the ensuing 3 hr. At 6 hr on the next day [NO3/NO2] values were lower than at tO and declined gradually during the next 4 hr. Leptin gradually declined from pre-operative concentrations, reaching a minimum at 3 hr and its concentration was unaffected by the bleeding stress of the second day. We conclude that release of TNF-alpha, [NO3/NO2], and leptin are neurally controlled since plasma levels of all three declined as a result of anesthesia. TNF-alpha secretion was remarkably stress responsive, whereas NO release appeared to be suppressed by the combined operative and bleeding stress, and leptin was stress unresponsive.
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PMID:Comparisons of the effects of anesthesia and stress on release of tumor necrosis factor-alpha, leptin, and nitric oxide in adult male rats. 1136 20

Leptin is thought to be involved in febrigenic signaling from the periphery to the brain. Zucker obese rats have a so-called fatty mutation in the leptin receptor gene and express a dysfunctional protein. Studies comparing the fever responses of fatty (fa/fa) rats and of their lean (Fa/Fa and Fa/fa) counterparts yield contradictory results. To resolve these contradictions, we evaluated the effect of fatty mutation on infectious and stress-associated fevers at thermoneutrality (29 degrees C) and in a cool environment (20 degrees C). Zucker fa/fa and Fa/? rats were infused with Escherichia coli lipopolysaccharide (LPS; 10 microg/kg) through a jugular catheter (infectious fever) or with saline through the catheter (control) or received a painful intramuscular injection of saline (stress fever). At thermoneutrality, the colonic temperature (T(c)) responses of fatty rats to all stimuli tested were no different from the responses of lean rats. In a cool environment, T(c) responses of fatty rats to all stimuli were ~0.5 degrees C lower than those of lean rats. The observed attenuation of LPS-induced and stress-associated fevers in Zucker fatty rats in the cold agrees with the literature data showing that brown adipose tissue (the major heat production effector) is morphologically and functionally defective in these rats. The normal febrile responses of fatty Zucker rats to pyrogenic stimuli at thermoneutrality indicate that fatty mutation does not interrupt febrigenic signaling from the periphery to the brain.
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PMID:Fever responses of Zucker rats with and without fatty mutation of the leptin receptor. 1174 53

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


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