title: Leptin is involved in age-dependent changes in response to systemic inflammation in the rat.
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 RT-PCR including inhibitor κBα, 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 (TNF)-α 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.
authors: Sandy
authors: S
authors: Koenig
authors: Giamal N
authors: GN
authors: Luheshi
authors: Tina
authors: T
authors: Wenz
authors: Rüdiger
authors: R
authors: Gerstberger
authors: Joachim
authors: J
authors: Roth
authors: Christoph
authors: C
authors: Rummel
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000375:Aging / Q000378:metabolism*; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000097:blood*; D007031:Hypothalamus / Q000378:metabolism; D007249:Inflammation / Q000097:blood / Q000378:metabolism*; D020738:Leptin / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D008099:Liver / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D016207:Cytokines; D020738:Leptin; D008070:Lipopolysaccharides; D035683:MicroRNAs; D051546:Cyclooxygenase 2; C489691:Ptgs2 protein, rat