Koenig, Sandy, Luheshi, Giamal N., Wenz, Tina, Gerstberger, Ruediger, Roth, Joachim and Rummel, Christoph (2014). Leptin is involved in age-dependent changes in response to systemic inflammation in the rat. Brain Behav. Immun., 36. S. 128 - 139. SAN DIEGO: ACADEMIC PRESS INC ELSEVIER SCIENCE. ISSN 1090-2139
Full text not available from this repository.Abstract
Obesity contributes to a state of subclinical peripheral and central inflammation and is often associated with aging. Here we investigated the source and contribution of adipose tissue derived cytokines and the cytokine-like hormone leptin to age-related changes in lipopolysaccharide (LPS)-induced brain-controlled sickness-responses. Old (24 months) and young (2 months) rats were challenged with LPS or saline alone or in combination with a neutralizing leptin antiserum (LAS) or control serum. Changes in the sickness-response were monitored by biotelemetry. Additionally, ex vivo fat-explants from young and old rats were stimulated with LPS or saline and culture medium collected and analyzed by cytokine-specific bioassays/ELISAs. We found enhanced duration/degree of the sickness-symptoms, including delayed but prolonged fever in old rats. This response was accompanied by increased plasma-levels of interleukin (IL)-6 and IL-1ra and exaggerated expression of inflammatory markers in brain and liver analyzed by RTPCR including inhibitor kappa B alpha, microsomal prostaglandin synthase and cyclooxygenase 2 (brain). Moreover, for the first time, we were able to show prolonged elevated plasma leptin-levels in LPS-treated old animals. Treatment with LAS in young rats tended to attenuate the early- and in old rats the prolonged febrile response. Fat-explants exhibited unchanged IL-6 but reduced IL-1ra and tumor necrosis factor (TNE)-alpha release from adipose tissue of aged compared to young animals. In addition, we found increased expression of the endogenous immune regulator microRNA146a in aged animals suggesting a role for these mediators in counteracting brain inflammation. Overall, our results indicate a role of adipose tissue and leptin in aging-related-inflammation and age-dependent modifications of febrile-responses. (C) 2013 Elsevier Inc. All rights reserved.
Item Type: | Journal Article | ||||||||||||||||||||||||||||
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URN: | urn:nbn:de:hbz:38-447341 | ||||||||||||||||||||||||||||
DOI: | 10.1016/j.bbi.2013.10.019 | ||||||||||||||||||||||||||||
Journal or Publication Title: | Brain Behav. Immun. | ||||||||||||||||||||||||||||
Volume: | 36 | ||||||||||||||||||||||||||||
Page Range: | S. 128 - 139 | ||||||||||||||||||||||||||||
Date: | 2014 | ||||||||||||||||||||||||||||
Publisher: | ACADEMIC PRESS INC ELSEVIER SCIENCE | ||||||||||||||||||||||||||||
Place of Publication: | SAN DIEGO | ||||||||||||||||||||||||||||
ISSN: | 1090-2139 | ||||||||||||||||||||||||||||
Language: | English | ||||||||||||||||||||||||||||
Faculty: | Unspecified | ||||||||||||||||||||||||||||
Divisions: | Unspecified | ||||||||||||||||||||||||||||
Subjects: | no entry | ||||||||||||||||||||||||||||
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URI: | http://kups.ub.uni-koeln.de/id/eprint/44734 |
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