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However, little is known about how postnatal overfeeding contributes to changes in the ability to respond to inflammation. In the present study, 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 being up to 0.5\u2003\u00b0C higher compared to those in controls, and this is associated with an enhanced pro\u2010inflammatory cytokine profile and enhanced hypothalamic\u2010pituitary\u2010adrenal (HPA) axis activation. Plasma pro\u2010inflammatory cytokines concentrations were approximately three\u2010fold greater in neonatally overfed rats after LPS and there were approximately twice as many neurones activated in the paraventricular nucleus of the hypothalamus as in controls, with a prolonged corticosterone response. We also observed elevated expression of toll\u2010like receptors (TLR) 2 and 4 in adipose tissue and greater inhibitory factor \u03baB 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 that 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\u2010regulated downstream pro\u2010inflammatory cascade.<\/jats:p>","DOI":"10.1111\/j.1365-2826.2011.02269.x","type":"journal-article","created":{"date-parts":[[2011,12,19]],"date-time":"2011-12-19T08:21:27Z","timestamp":1324282887000},"page":"511-524","source":"Crossref","is-referenced-by-count":57,"title":["Postnatal Overfeeding Leads to Obesity and Exacerbated Febrile Responses to Lipopolysaccharide Throughout Life"],"prefix":"10.1111","volume":"24","author":[{"given":"M. A.","family":"Clarke","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Stefanidis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. 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