title: Leptin fails to blunt the lipopolysaccharide-induced activation of the hypothalamic-pituitary-adrenal axis in rats.
abstract: 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.
authors.affiliation: Division of Diabetes, Endocrinology and Metabolism, Department of Investigative Medicine, Imperial College London, Hammersmith Hospital Campus, 6th Floor, Commonwealth Building, Du Cane Road, London W12 0NN, UK University College London, Institute of Neurology, Queen Square House, Queen Square, London WC1N 3BG, UK Brunel University, Wilfred Brown Building, Kingston Lane, Uxbridge UB8 3PH, UK.
authors.forename: Saadia
authors.initials: S
authors.lastname: Basharat
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Parker
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Murphy
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Bloom
authors.forename: Julia C
authors.initials: JC
authors.lastname: Buckingham
authors.forename: Christopher D
authors.initials: CD
authors.lastname: John
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D020738:Leptin / Q000008:administration & dosage* / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D018805:Sepsis / Q000378:metabolism / Q000517:prevention & control*
chemical_list: D020738:Leptin; D008070:Lipopolysaccharides; D000324:Adrenocorticotropic Hormone
keywords: HPA; leptin; sepsis; stress