The effect of fasting on anti-inflammatory mediators, IL-1RA and IL-1R2, and their role in resistance to sickness behaviors in mice

Dietary regimens involving fasting have long been linked to beneficial health outcomes including; reduction in heart disease, diabetes, improved mood and cognition, and resistance to sickness behaviors such as anorexia and fever. The mechanisms underlying fasting-induced health benefits and alterations in immunity and sickness behavior continues to remain debated despite over 20 years of interest. This research project confirms that acute dietary restriction (24 h water-only fast) is able to attenuate IL-1β-induced anorexia, in addition to other sickness behaviors at early stages of the acute phase response. We previously reported that fasting was able to reduce gene expression of inflammatory IL-1α in the brain, here we looked at liver and adipose in addition to brain and uncovered a major up-regulation of IL-1 endogenous inhibitors, IL-1RA and IL-1R2 in peripheral tissues. These findings imply that attenuation in sickness behaviors observed may be due to counter-regulation of IL-1 via up-regulation of IL-1R2 and/or IL-1RA shown in metabolically active organs, which is capable of blunting the centrally-mediated effects of induced peripheral challenge. Our results further demonstrate that the mechanisms involved in IL-1R2 and IL-1RA up-regulation are independent of IL-1, TLR-4, IL-4 and glucocordicoid signaling. Here we also demonstrate that free fatty acids (FFA) are increased in the plasma as a consequence of fasting. Using palmitic acid injection to mimic fastings FFA increase, we elucidated a novel mechanism by which IL-1R2 is up-regulated. This method showed increased IL-1R2 gene transcripts in the liver of mice. FFA signaling, which produces an immune response, is shown here to be TLR-4-independent, implicating free fatty acid receptor 1 (FFAR1) as the key signaling receptor initiating the anti-inflammatory result of fasting documented in this study.

Name thesis:degree_name

M.S.

Level thesis:degree_level

Thesis

Discipline thesis:degree_discipline

Animal Sciences

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Joesting, Jennifer J.

Contributors dc:contributor

• Freund, Gregory G.

• Fasting
• Dietary Restriction
• Anti-inflammation
• Interleukin 1 Receptor Type 2 (IL-1R2)
• Interleukin 1 Receptor Antagonist (IL-1RA)
• sickness behavior
• IL-1 decoy receptor
• Free Fatty Acids (FFA)
• Non-Esterified Fatty Acids (NEFA)

Statement dc:rights

• Copyright 2013 Jennifer J. Joesting

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/44463

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/44463