Systemic administration of lipopolysaccharide increases plasma leptin levels

Francis, Joseph; MohanKumar, P.S.; MohanKumar, Sheba M.J.; Quadri, S. K.

doi:10.1007/bf02738628

Cited by 52 publications

(30 citation statements)

References 38 publications

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“…LPS increases leptin (23), which in turn induces POMC activation (20). The CR50% animals in the present study demonstrated an attenuation of leptin expression at 2 h post-LPS.…”

Section: Cr Sickness Behavior and A Potential Mechanismsupporting

confidence: 53%

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

MacDonald

Radler

Paolini

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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MacDonald L, Radler M, Paolini AG, Kent S. Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias. Am J Physiol Regul Integr Comp Physiol 301: R172-R184, 2011. First published April 27, 2011 doi:10.1152/ajpregu.00057.2011 has been demonstrated to alter cytokine levels; however, its potential to modify sickness behavior (fever, anorexia, cachexia) has not. The effect of CR on sickness behavior was examined in male C57BL/6J mice fed ad libitum or restricted 25% (CR25%) or restricted 50% (CR50%) in food intake for 28 days and injected with 50 g/kg of LPS on day 29. Changes in body temperature, locomotor activity, body weight, and food intake were determined. A separate cohort of mice were fed ad libitum or CR50% for 28 days, and hypothalamic mRNA expression of inhibitory factor B-␣ (I B-␣), cyclooxygenase-2 (COX-2), prostaglandin E 2 (PGE2), suppressor of cytokine signaling 3 (SOCS3), IL-10, neuropeptide Y (NPY), leptin, proopiomelanocortin (POMC), and corticotrophin-releasing hormone (CRH) were determined at 0, 2, and 4 h post-LPS. CR50% mice did not develop fevers, whereas the CR25% mice displayed a fever shorter in duration but with the same peak as the controls. Both CR25% and CR50% mice showed no sign of anorexia and reduced cachexia after LPS administration. Hypothalamic mRNA expression of NPY and CRH were both increased by severalfold in CR50% animals preinjection compared with controls. The CR50% mice did not demonstrate the expected rise in hypothalamic mRNA expression of COX-2, microsomal prostaglandin E synthase-1, POMC, or CRH 2 h post-LPS, and leptin expression was decreased at this time point. Increases in SOCS3, IL-10, and I B-␣ expression in CR50% animals were enhanced compared with ad libitum-fed controls at 4 h post-LPS. CR results in a suppression of sickness behavior in a dose-dependent manner, which may be due to CR attenuating proinflammatory pathways and enhancing anti-inflammatory pathways. fever; suppressor of cytokine signaling 3; cyclooxygenase-2; microsomal prostaglandin E synthase-1; leptin CALORIE RESTRICTION (CR), a dietary regimen low in calories, while avoiding malnutrition, is the only manipulation that has consistently been shown to extend the mean and maximum life span in a range of species (2,42,71,76). In addition to an increase in life span, CR attenuates the normal immunosenscence seen with age (52), along with reducing the occurrence of other age-related diseases (14,39,43,53,54,79).It has been postulated that the mechanism by which CR extends the mean and maximum life span is by reducing oxidative stress caused by unregulated increases in reactive oxygen species (3,19,31,42,69), as well as by limiting the age-related increase in basal pro-inflammatory cytokine levels (73). One possible mechanism by which CR exerts its antiinflammatory effect are glucocorticoids, which are increased after CR (33, 47) and act to increase the transcription of anti-inflammatory cytokines and decrease the transcripti...

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“…LPS increases leptin (23), which in turn induces POMC activation (20). The CR50% animals in the present study demonstrated an attenuation of leptin expression at 2 h post-LPS.…”

Section: Cr Sickness Behavior and A Potential Mechanismsupporting

confidence: 53%

Calorie restriction attenuates LPS-induced sickness behavior and shifts hypothalamic signaling pathways to an anti-inflammatory bias

MacDonald

Radler

Paolini

et al. 2011

American Journal of Physiology-Regulatory, Integrative and Comp

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“…activated cytokine production in the brain and at the periphery including in adipose tissue, liver, and spleen. In another study, LPSinduced leptin release was mediated through IL-1␤ because a soluble IL-1␤ receptor antagonist completely blocked the LPS-induced increase in the leptin levels (Francis et al, 1999). Thus, we can conclude that Hp-LPS-induced protection and adaptation resulting in the limitation of ASA damage may depend upon leptin expression and release and, as shown in this study, could also be mediated by neuropeptides released from sensory afferent nerves.…”

Section: Discussionsupporting

confidence: 68%

Involvement of Capsaicin-Sensitive Afferent Nerves and Cholecystokinin 2/Gastrin Receptors in Gastroprotection and Adaptation of Gastric Mucosa toHelicobacter pylori-Lipopolysaccharide

Brzozowski

Konturek²,

Moran³

et al. 2004

J Pharmacol Exp Ther

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Lipopolysaccharide (LPS) is one of the virulence factors in theHelicobacter pylori (Hp)-infected stomach, but it remains unknown whether single and prolonged pretreatment with Hp-LPS can affect the course of gastric damage induced by aspirin (ASA). We compared the effects of Hp-LPS with those induced by LPSs isolated from intestinal Bacteroides fragilis, Yersinia enterocolitica, and Campylobacter jejuni applied for 4 days on acute ASA-induced gastric lesions in rats. The area of ASAinduced gastric lesions, gastric blood flow (GBF), expression of mRNA and protein of leptin and plasma leptin, gastrin, interleukin-1␤, and tumor necrosis factor-␣ levels were examined. Single (once) or repeated (five times) i.p. injections of Hp-LPS (1 mg/kg) or intestinal LPSs failed to produce macroscopic gastric damage and did not affect the GBF when compared with vehicle. Hp-LPS injected repeatedly suppressed the gastric acid secretion, up-regulated leptin mRNA and protein, and increased plasma leptin and gastrin levels. Hp-LPS significantly reduced the ASA-induced gastric damage and the accompanying decline in the GBF, and these effects were significantly attenuated by capsaicin denervation and selective antagonism of cholecystokinin-B (CCK 2 ) receptors by RPR-102681 [N-(metoxy-3 phenyl) N-(N-methyl N-phenyl-carbamylmethyl) carbamoylmethyl]-3 ureido}-3 phenyl}-2 propronique] but not by loxiglumide, an antagonist of CCK 1 receptors. We conclude that 1) daily application of Hp-LPS enhances gastric mucosal resistance against ASA damage due to the increase of GBF and the expression and release of leptin and gastrin exerting trophic and gastroprotective effects, and 2) this enhanced resistance to ASA damage in Hp-LPS-adapted stomach is mediated by the sensory afferents and specific CCK 2 /gastrin receptors.Helicobacter pylori (Hp) is now generally accepted as a major cause of chronic gastritis and an important risk factor for peptic ulcer disease and gastric cancer (Warren and Marshall, 1983;Konturek et al., 1999), but it remains unknown whether the gastric mucosa is capable of adapting to repeated Hp insults and whether such Hp adaptation might alter the mucosal resistance to the injurious action of strong irritants.Various pathogenic factors originating from Hp have been implicated in the damaging effect of this bacterium on the gastric mucosa, the most important in addition to ammonia being cytotoxins released by Hp strains expressing the vacuolating cytotoxin A and cytotoxin-associated gene A proteins, Hp-derived lipopolysaccharides (Hp-LPSs), and the enhanced generation of reactive oxygen species (Megraud et al., 1992;Crabtree, 1996;Figura and Tabaqchali, 1996; Moran, 2001a,b). Hp-LPS exhibits a low immunological activity, and this property has been assumed to play an important role in the persistency of Hp infection in the human stomach (Moran, 2001a,b). Nevertheless, the deleterious action of LPS derived from Hp in the stomach includes an interaction of this endotoxin with laminin (Valkonen et al., 1994), its influe...

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“…Its plasma levels are directly correlated with adipose tissue mass and act at hypothalamic central level as a satiety factor inducing a decrease in food intake and an increase in energy consumption [3]. Several studies have demonstrated that acute infection, sepsis, and a wide range of inflammatory mediators increase serum leptin levels, suggesting that leptin is a part of the immune response and host defense mechanisms [4][5][6]. It has been reported that circulating leptin levels are highly and promptly increased in experimental models of acute inflammation [7].…”

Section: Introductionmentioning

confidence: 99%