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

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)

Joesting, Jennifer J. ; Freund ; Gregory G.

关键词: 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);   

Others  :  https://www.ideals.illinois.edu/bitstream/handle/2142/44463/Jennifer_Joesting.pdf?sequence=1&isAllowed=y

美国|英语

来源: The Illinois Digital Environment for Access to Learning and Scholarship

【 摘 要 】

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.