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 Derous, Sharon E. Mitchell, Cara L. Green, Luonan Chen, Jing-Dong J. Han, Yingchun Wang, Daniel E. L. Promislow, David Lusseau, John R. Speakman (Corresponding Author), Alex Douglas (Corresponding Author)

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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.
Original languageEnglish
Pages (from-to)642-661
Number of pages20
JournalAging
Volume8
Issue number4
Early online date23 Feb 2016
DOIs
Publication statusPublished - Apr 2016

Fingerprint

Hunger
Somatomedins
Circadian Rhythm
Leptin
Tumor Necrosis Factor-alpha
Hormones
Insulin
Genes
Response Elements
Neuropeptides
Body Temperature
Inbred C57BL Mouse
Up-Regulation
Eating
Phenotype
Food

Keywords

  • calorie restriction
  • circadian rhythm
  • hunger
  • Hypothalamus
  • transcriptomics

Cite this

@article{0519dfdf6da54924b52abdf6ba4f01d2,
title = "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",
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.",
keywords = "calorie restriction, circadian rhythm, hunger, Hypothalamus, transcriptomics",
author = "Davina Derous and Mitchell, {Sharon E.} and Green, {Cara L.} and Luonan Chen and Han, {Jing-Dong J.} and Yingchun Wang and Promislow, {Daniel E. L.} and David Lusseau and Speakman, {John R.} and Alex Douglas",
note = "Acknowledgements We would like to acknowledge the BSU staff for their invaluable help with caring for the animals. Funding The work was supported by the UK Biotechnology and Biological Sciences Research Council BBSRC (BB/G009953/1 and BB/J020028/1) to JRS and SEM and a studentship of DD supported by the Centre for Genome Enabled Biology and Medicine, Aberdeen, UK. Joint meetings were funded by BBSRC grant (China partnering award BB/JO20028/1).",
year = "2016",
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doi = "10.18632/aging.100895",
language = "English",
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journal = "Aging",
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publisher = "IMPACT JOURNALS LLC",
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TY - JOUR

T1 - The effects of graded levels of calorie restriction

T2 - VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways

AU - Derous, Davina

AU - Mitchell, Sharon E.

AU - Green, Cara L.

AU - Chen, Luonan

AU - Han, Jing-Dong J.

AU - Wang, Yingchun

AU - Promislow, Daniel E. L.

AU - Lusseau, David

AU - Speakman, John R.

AU - Douglas, Alex

N1 - Acknowledgements We would like to acknowledge the BSU staff for their invaluable help with caring for the animals. Funding The work was supported by the UK Biotechnology and Biological Sciences Research Council BBSRC (BB/G009953/1 and BB/J020028/1) to JRS and SEM and a studentship of DD supported by the Centre for Genome Enabled Biology and Medicine, Aberdeen, UK. Joint meetings were funded by BBSRC grant (China partnering award BB/JO20028/1).

PY - 2016/4

Y1 - 2016/4

N2 - 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.

AB - 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.

KW - calorie restriction

KW - circadian rhythm

KW - hunger

KW - Hypothalamus

KW - transcriptomics

U2 - 10.18632/aging.100895

DO - 10.18632/aging.100895

M3 - Article

VL - 8

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EP - 661

JO - Aging

JF - Aging

SN - 1945-4589

IS - 4

ER -