Leptin is involved in age-dependent changes in response to systemic inflammation in the rat

Brain Behav Immun. 2014 Feb;36:128-38. doi: 10.1016/j.bbi.2013.10.019.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism
  • Aging / metabolism*
  • Animals
  • Cyclooxygenase 2 / metabolism
  • Cytokines / blood*
  • Hypothalamus / metabolism
  • Inflammation / blood
  • Inflammation / metabolism*
  • Leptin / physiology*
  • Lipopolysaccharides / toxicity
  • Liver / metabolism
  • Male
  • MicroRNAs / metabolism
  • Oxidative Stress
  • Rats
  • Rats, Wistar

Substances

  • Cytokines
  • Leptin
  • Lipopolysaccharides
  • MicroRNAs
  • Cyclooxygenase 2
  • Ptgs2 protein, rat