Document Detail

Postnatal overfeeding leads to obesity and exacerbated febrile responses to lipopolysaccharide throughout life.
MedLine Citation:
PMID:  22175701     Owner:  NLM     Status:  Publisher    
The perinatal environment can be crucial for programming long-term physiology, including the mechanisms regulating body weight and postnatal overfeeding can lead to obesity throughout life. Inflammation-related complications are of particular concern in the obese. However, little is known about how postnatal overfeeding contributes to changes in the ability to respond to inflammation. Here we investigate changes in the febrile and neurochemical response to immune challenge with lipopolysaccharide (LPS), in juvenile and adult, male, and female Wistar rats made obese by overfeeding during the postnatal period. We demonstrate that febrile responses to LPS are exacerbated in these rats, with peak core temperatures reaching 0.5 °C higher than in controls, and this is associated with an enhanced pro-inflammatory cytokine profile and enhanced hypothalamic-pituitary-adrenal (HPA) axis activation. Plasma pro-inflammatory cytokines concentrations were ∼ three times greater in neonatally overfed rats after LPS and there were ∼ twice as many neurons activated in the paraventricular nucleus of the hypothalamus as in controls, with a prolonged corticosterone response. We also saw elevated expression of toll-like receptor (TLR) 2 and 4 in adipose tissue and greater inhibitory factor κB phosphorylation in these obese animals. Despite similar changes in expression of adipose TLR3, there was no corresponding alteration in the response to a viral mimetic that acts at this receptor. We suggest an elevated febrile response to LPS therefore occurs in cases of obesity and this is associated with altered HPA axis function and enhanced TLR2/4 expression in adipose tissue and an up-regulated downstream pro-inflammatory cascade.
Melanie A Clarke; Aneta Stefanidis; Sarah J Spencer
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-19
Journal Detail:
Title:  Journal of neuroendocrinology     Volume:  -     ISSN:  1365-2826     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-19     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8913461     Medline TA:  J Neuroendocrinol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal of Neuroendocrinology © 2011 Blackwell Publishing.
Department of Physiology, Faculty of Medicine, Monash University, Melbourne, Vic., Australia 3800.
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