Cargando…

Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats

Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as...

Descripción completa

Detalles Bibliográficos
Autores principales: Basharat, Saadia, Parker, Jennifer A, Murphy, Kevin G, Bloom, Stephen R, Buckingham, Julia C, John, Christopher D
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Bioscientifica Ltd 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045222/
https://www.ncbi.nlm.nih.gov/pubmed/24578293
http://dx.doi.org/10.1530/JOE-13-0249
_version_ 1782319276465586176
author Basharat, Saadia
Parker, Jennifer A
Murphy, Kevin G
Bloom, Stephen R
Buckingham, Julia C
John, Christopher D
author_facet Basharat, Saadia
Parker, Jennifer A
Murphy, Kevin G
Bloom, Stephen R
Buckingham, Julia C
John, Christopher D
author_sort Basharat, Saadia
collection PubMed
description Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis. We hypothesised that leptin would attenuate the HPA axis response to sepsis. We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1β secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats.
format Online
Article
Text
id pubmed-4045222
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher Bioscientifica Ltd
record_format MEDLINE/PubMed
spelling pubmed-40452222014-06-05 Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats Basharat, Saadia Parker, Jennifer A Murphy, Kevin G Bloom, Stephen R Buckingham, Julia C John, Christopher D J Endocrinol Research Obesity is a risk factor for sepsis morbidity and mortality, whereas the hypothalamic–pituitary–adrenal (HPA) axis plays a protective role in the body's defence against sepsis. Sepsis induces a profound systemic immune response and cytokines serve as excellent markers for sepsis as they act as mediators of the immune response. Evidence suggests that the adipokine leptin may play a pathogenic role in sepsis. Mouse endotoxaemic models present with elevated leptin levels and exogenously added leptin increased mortality whereas human septic patients have elevated circulating levels of the soluble leptin receptor (Ob-Re). Evidence suggests that leptin can inhibit the regulation of the HPA axis. Thus, leptin may suppress the HPA axis, impairing its protective role in sepsis. We hypothesised that leptin would attenuate the HPA axis response to sepsis. We investigated the direct effects of an i.p. injection of 2 mg/kg leptin on the HPA axis response to intraperitoneally injected 25 μg/kg lipopolysaccharide (LPS) in the male Wistar rat. We found that LPS potently activated the HPA axis, as shown by significantly increased plasma stress hormones, ACTH and corticosterone, and increased plasma interleukin 1β (IL1β) levels, 2 h after administration. Pre-treatment with leptin, 2 h before LPS administration, did not influence the HPA axis response to LPS. In turn, LPS did not affect plasma leptin levels. Our findings suggest that leptin does not influence HPA function or IL1β secretion in a rat model of LPS-induced sepsis, and thus that leptin is unlikely to be involved in the acute-phase endocrine response to bacterial infection in rats. Bioscientifica Ltd 2014-05 /pmc/articles/PMC4045222/ /pubmed/24578293 http://dx.doi.org/10.1530/JOE-13-0249 Text en © 2014 The authors http://creativecommons.org/licenses/by/3.0/deed.en_GB This work is licensed under a Creative Commons Attribution 3.0 Unported License (http://creativecommons.org/licenses/by/3.0/deed.en_GB)
spellingShingle Research
Basharat, Saadia
Parker, Jennifer A
Murphy, Kevin G
Bloom, Stephen R
Buckingham, Julia C
John, Christopher D
Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
title Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
title_full Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
title_fullStr Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
title_full_unstemmed Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
title_short Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
title_sort leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic–pituitary–adrenal axis in rats
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4045222/
https://www.ncbi.nlm.nih.gov/pubmed/24578293
http://dx.doi.org/10.1530/JOE-13-0249
work_keys_str_mv AT basharatsaadia leptinfailstobluntthelipopolysaccharideinducedactivationofthehypothalamicpituitaryadrenalaxisinrats
AT parkerjennifera leptinfailstobluntthelipopolysaccharideinducedactivationofthehypothalamicpituitaryadrenalaxisinrats
AT murphykeving leptinfailstobluntthelipopolysaccharideinducedactivationofthehypothalamicpituitaryadrenalaxisinrats
AT bloomstephenr leptinfailstobluntthelipopolysaccharideinducedactivationofthehypothalamicpituitaryadrenalaxisinrats
AT buckinghamjuliac leptinfailstobluntthelipopolysaccharideinducedactivationofthehypothalamicpituitaryadrenalaxisinrats
AT johnchristopherd leptinfailstobluntthelipopolysaccharideinducedactivationofthehypothalamicpituitaryadrenalaxisinrats