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Title:Immunological and behavioral consequences of high-fat diet feeding in mice
Author(s):Lavin, Desiree N.
Advisor(s):Freund, Gregory G.
Department / Program:Nutritional Sciences
Discipline:Nutritional Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
high-fat diet
saccharin preference
Interleukin 1 receptor antagonist (IL-1RA)
Abstract:Obesity is a harmful and costly condition which continues to increase in prevalence. Co-morbidities accompanying this disease include brain-based disorders that impact cognition and mood. Anhedonia is a biobehavior associated with depression that manifests in mice as a loss of interest in consuming a highly palatable sucrose or saccharin solution. Here we show that obese mice fed a high-fat diet (HFD), fail to exhibit an interest in saccharin (27% vs 74%) compared to mice fed a low-fat diet (LFD) (p < 0.007). When HFD mice undergo a fasting period of 24 hours, saccharin preferences equilibrate to water consumption (51% saccharin vs 49% water). Other behaviors such as immobility during the forced swim test (FST) and burrowing behavior are improved by fasting in HFD mice. We have previously shown and demonstrate here that basal serum leptin and IL-1RA concentrations are increased in mice fed HFD for 12 weeks compared to mice fed LFD. Leptin has been associated with modulation of motivation to obtain reward and anti-depressant activity, and IL-1RA has been implicated in the mediation of central leptin resistance. To examine if these cytokines contributed to the increased saccharin consumption and other behaviors observed in fasted HFD mice, we measured serum concentrations during the fed and fasted states. Leptin decreased, although not significantly, in mice fed a HFD (43,844 vs 42,791 pg/mL) and LFD (8,118 vs 3,104 pg/mL) after a 24-hour fast. IL-1RA did not significantly change in either group fed LFD or HFD when fasted, and IL-1β was not detectable in any group. We further investigated differences in leptin, leptin receptor (LepR), IL-1RA, IL-1R1, IL-1R2, IL1α and IL-1β brain expression in fed and fasted HFD and LFD mice utilizing real-time PCR (RT PCR) gene expression analysis. A 2-fold increase in leptin expression was seen in both LFD (1 vs 2) and HFD (2 vs 4) after a 24 hour fast (p < 0.05). IL-1RA expression was increased 2.3-fold in HFD compared to LFD in the fed state (1 ± 0.31 vs 2.26 ± 0.66) (p < 0.05) and trended toward increasing in the HFD fed vs fasted (1.89 vs 4.16) but this was not significant. IL-1R1 expression was decreased in fed (0.79 ± 0.09 vs 1 ± 0.08) and fasted (0.68 ± 0.14 vs 0.88 ± 0.07; p < 0.05) HFD mice compared to LFD mice. IL-1R2 expression was decreased during fasting in mice fed HFD compared to mice fed LFD (1.013 ± 0.12 vs. 1.40 ± 0.08; p < 0.005). IL-1α expression was increased 1.5-fold after fasting in mice fed HFD compared to mice fed LFD (0.923 ± 0.14 vs. 0.59 ± 0.15; p < 0.05) and decreased by 1.6-fold during fasting within the LFD group compared to its fed state (0.6 ± 0.15 vs 1 ± 0.19; p < 0.05). Taken together, these data show that changes in brain gene expression of leptin, IL-1α, IL-1R2, IL-1R1 and IL-1RA occur during fasting, and that these changes may be affected by nutritional status and contribute to differences in saccharin preference in mice fed a HFD. In order to determine if IL-1RA played a role in saccharin consumption, IL-1RA knockout mice were given a saccharin preference test. Similar to mice fed HFD, IL-1RA KO mice had an aversion to saccharin compared to control WT mice. IL-1RA KO mice consumed 12% saccharin solution compared to control WT mice that consumed 65% of their total daily fluid intake from saccharin solution (p < 0.005). Taken together, these data indicate that a deviation in normal levels of brain IL-1RA may contribute to saccharin aversion, and that fasting has a behavioral benefit in mice fed HFD that may be reliant on increased leptin expression in the brain.
Issue Date:2010-05-18
Rights Information:Copyright 2010 Desiree N. Lavin
Date Available in IDEALS:2010-05-18
Date Deposited:May 2010

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