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Research Paper|Volume 8, Issue 4|pp 642—661

The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

Davina Derous1,2, Sharon E. Mitchell1, Cara L. Green1, Luonan Chen3, Jing‐Dong J. Han4, Yingchun Wang5, Daniel E.L. Promislow6, David Lusseau1, John R. Speakman1,5, Alex Douglas1,2
  • 1Institute of Biological and Environmental Sciences, University of Aberdeen, Aberdeen, Scotland, AB24 2TZ, UK
  • 2Centre for Genome Enabled Biology and Medicine, University of Aberdeen, Aberdeen, Scotland, AB24 3RL, UK
  • 3Key laboratory of Systems Biology, Innovation Center for Cell Signaling Network, Institute of Biochemistry and Cell Biology, Shanghai Institute of Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
  • 4Chinese Academy of Sciences Key Laboratory of Computational Biology, Chinese Academy of Sciences‐Max Planck Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, 200031, China
  • 5State Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Chaoyang, Beijing, 100101, China
  • 6Department of Pathology and Department of Biology, University of Washington at Seattle, Seattle, WA 98195, USA

* * Equal contribution

Received: October 29, 2015Accepted: January 20, 2016Published: February 23, 2016
https://doi.org/10.18632/aging.100895

Copyright: © 2016 Derous et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti‐ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin‐like growth factor 1 (IGF‐1), insulin, and tumor necrosis factor alpha (TNF‐α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF‐α, leptin and IGF‐1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.