{"id":{"repo_id":"uiuc","oai_identifier":"oai:www.ideals.illinois.edu:2142/44463"},"canonical_url":"https://search.dev.ndltd.org/etd/uiuc/oai:www.ideals.illinois.edu:2142/44463","repository":{"repo_id":"uiuc","name":"University of Illinois - Urbana-Champaign","base_url":"https://www.ideals.illinois.edu/oai-pmh"},"display":{"title":"The effect of fasting on anti-inflammatory mediators, IL-1RA and IL-1R2, and their role in resistance to sickness behaviors in mice","abstract":"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.","abstract_html":"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.","abstract_has_math":false,"creators":["Joesting, Jennifer J."],"institution":"University of Illinois at Urbana-Champaign","degree_name":"M.S.","degree_level":"Thesis","degree_discipline":"Animal Sciences","degree_department":null,"school":null,"contributors":["Freund, Gregory G."],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2013,"date_issued":"2013-05-24T22:16:56Z","date_published":"2013-05-24T22:16:56Z","updated_at":"2026-07-22T22:25:34Z","subjects":["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)"],"languages":["en"],"rights":["Copyright 2013 Jennifer J. 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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.","Item withdrawn by Alexis Thompson (athmpsn1@illinois.edu) on 2013-04-18T14:16:43Z Item was in collections: University of Illinois Theses & Dissertations (ID: 1) No. of bitstreams: 1 Joesting_Jennifer.pdf: 734521 bytes, checksum: 83bedbcb0423a9d681c508b285a82ed7 (MD5)","Made available in DSpace on 2013-05-24T22:16:56Z (GMT). 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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. 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