The effects of melanocortin agonists and antagonists on leptin-induced fever in rats

Turek, Victoria F.; Olster, Deborah H.; Gililland, Katherine R.; Sheehy, Meredith; Ettenberg, Aaron; Carlisle, Harry J.

doi:10.1016/j.jtherbio.2004.08.011

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…Others have also reported that the i.c.v. injection of leptin or leptin anti-idiotype antibody that functionally mimics the action of leptin induced a similar increase in core body temperature (De Fanti et al, 2002;Turek et al, 2004), and that leptin enhanced PGE2 and PGF2a release from neonatal rat hypothalamic slices ex vivo (Brunetti et al, 1999). Finally, recent observations by us and others showing that the neutralization of endogenous leptin with LAS, as opposed to using recombinant protein, resulted in the attenuation of LPS-induced fever (Sachot et al, 2004;Harden et al, 2006), strongly support the pyrogenic effects of leptin.…”

Section: Discussionmentioning

confidence: 63%

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Leptin induces cyclooxygenase‐2 via an interaction with interleukin‐1β in the rat brain

Inoue

Poole

Bristow

et al. 2006

Eur J of Neuroscience

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In addition to its central effects on appetite regulation, leptin has been implicated in immune function and inflammation. Previous data suggested that leptin acts as an inflammatory signal within the brain, as exogenously administered leptin induced fever, a typical brain-regulated inflammatory response. The present study aimed to delineate the inflammatory actions and cellular targets of leptin in the brain by examining its effects on the expression of interleukin (IL)-1beta and cyclooxygenase (COX)-2, two important inflammatory components of the fever response. Intracerebroventricular injection of leptin (5 microg/rat) induced IL-1beta and COX-2 mRNA and protein in the hypothalamus between 1 and 3 h after treatment as determined by reverse transcription-polymerase chain reaction and immunohistochemistry. Coinjection of IL-1 receptor antagonist (100 microg/rat, intracerebroventricular) attenuated leptin-induced COX-2, whereas IL-1 receptor antagonist had no effect on endogenous IL-1beta levels, suggesting that leptin induces COX-2 via, at least partly, IL-1beta action. IL-1beta protein expression was induced in macrophages in the meningis and perivascular space after leptin treatment, whereas COX-2 induction was observed in endothelial cells, indicating the roles for these non-neuronal cells in mediating inflammatory actions of leptin. In addition, neutralization of endogenous circulating leptin with anti-leptin antiserum attenuated intraperitoneal lipopolysaccharide (100 microg/kg)-induced brain IL-1beta and COX-2 upregulation, suggesting that leptin indeed acts as an inflammatory signal to the brain during systemic inflammation. These findings are in contrast to the effects of leptin on appetite regulation where it is believed to act primarily on neurons, thus presenting a distinct anatomical basis for the inflammatory and appetite regulatory actions of leptin in the brain.

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Section: Discussionmentioning

confidence: 63%

“…injection of leptin or leptin anti‐idiotype antibody that functionally mimics the action of leptin induced a similar increase in core body temperature (De Fanti et al. , 2002; Turek et al. , 2004), and that leptin enhanced PGE2 and PGF2α release from neonatal rat hypothalamic slices ex vivo (Brunetti et al.…”

Section: Discussionmentioning

confidence: 87%

Leptin induces cyclooxygenase‐2 via an interaction with interleukin‐1β in the rat brain

Inoue

Poole

Bristow

et al. 2006

Eur J of Neuroscience

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“…Mechanisms that trigger warmth‐seeking behavior and fever when energy stores are high, but cold‐seeking behavior and hypothermia when energy stores are low, are likely to involve leptin. Indeed, the size of energy stores (fat depot) positively correlates with the plasma level of leptin (Frederich et al ., 1995; Saladin et al ., 1995; Considine et al ., 1996); decreased leptin signaling has been shown to promote LPS hypothermia (Steiner et al ., 2004) and to decrease LPS fever in rats (Sachot et al ., 2004); whereas increased leptin signaling has been demonstrated to cause fever in rats (Luheshi et al ., 1999; Turek et al ., 2004).…”

Section: Discussionmentioning

confidence: 99%

Cold‐seeking behavior as a thermoregulatory strategy in systemic inflammation

Almeida¹,

Steiner²,

Branco³

et al. 2006

Eur J of Neuroscience

132

129

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Systemic inflammation (SI) is a leading cause of hospital death. Although fever and hypothermia are listed as symptoms in every definition of SI, how SI affects thermoregulatory behavior is unclear. SI is often modeled by systemic administration of bacterial lipopolysaccharide (LPS) to rats. When rats are not allowed to regulate their body temperature (Tb) behaviorally, LPS causes either fever or hypothermia, and the direction of the response is determined by LPS dose and ambient temperature (Ta). However, in many studies in which rats were allowed to regulate Tb behaviorally (by selecting their preferred Ta in a thermogradient apparatus), they consistently expressed warmth-seeking behavior and developed fever. We hypothesized that SI can cause not only warmth-seeking behavior but also cold-seeking behavior; we then tested this hypothesis by studying LPS-induced thermoregulatory behavior in adult Wistar rats. A multichannel thermogradient apparatus, implantable data loggers and infrared thermography were used; multiple control experiments were conducted; and the ability of the apparatus to reliably register the changes in rats' preferred Ta induced by thermal (external cooling or heating) or chemical (TRPV1 or TRPM8 agonist) stimuli was confirmed. The rats responded to a low dose of LPS (10 microg/kg i.v.) with warmth-seeking behavior and a polyphasic fever, but to a high dose (5 mg/kg i.v.) with marked cold-seeking behavior and hypothermia followed by warmth-seeking behavior and fever. This is the first well-controlled study to report SI-associated cold-seeking behavior in rats. Cold-seeking behavior is likely to be an important defense response in severe SI.

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“…Inflammatory stimuli (e.g., TNFa, IL-1b, LPS, and TURP) in turn increase leptin synthesis (163)(164)(165)(166)(167). During the acute inflammatory response, leptin is involved in the induction of several sickness-type responses, such as anorexia and fever (168)(169)(170)(171)(172)(173).…”

Section: Leptinmentioning

confidence: 99%

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

2020

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Prenatal infections have been linked to the development of schizophrenia (SCZ) and other neurodevelopmental disorders in the offspring, and work in animal models indicates that this is to occur through the maternal inflammatory response triggered by infection. Several studies in animal models demonstrated that acute inflammatory episodes are sufficient to trigger brain alterations in the adult offspring, especially in the mesolimbic dopamine (DA) system, involved in the pathophysiology of SCZ and other disorders involving psychosis. In the current review, we synthesize the literature on the clinical studies implicating prenatal infectious events in the development of SCZ. Then, we summarize evidence from animal models of maternal immune activation (MIA) and the behavioral and molecular alterations relevant for the function of the DAergic system. Furthermore, we discuss the evidence supporting the involvement of maternal cytokines, such as interleukin 6 (IL-6) and leptin (a hormone with effects on inflammation) in mediating the effects of MIA on the fetal brain, leading to the long-lasting effects on the offspring. In particular, IL-6 has been involved in mediating the effects of MIA animal models in the offspring through actions on the placenta, induction of IL-17a, or triggering the decrease in non-heme iron (hypoferremia). Maternal infection is very likely interacting with additional genetic and environmental risk factors in the development of SCZ; systematically investigating how these interactions produce specific phenotypes is the next step in understanding the etiology of complex psychiatric disorders.

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The effects of melanocortin agonists and antagonists on leptin-induced fever in rats

Cited by 7 publications

References 38 publications

Leptin induces cyclooxygenase‐2 via an interaction with interleukin‐1β in the rat brain

Leptin induces cyclooxygenase‐2 via an interaction with interleukin‐1β in the rat brain

Cold‐seeking behavior as a thermoregulatory strategy in systemic inflammation

Maternal Immune Activation and the Development of Dopaminergic Neurotransmission of the Offspring: Relevance for Schizophrenia and Other Psychoses

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