Abstract
| Original language | English |
|---|---|
| Pages (from-to) | 642-661 |
| Number of pages | 20 |
| Journal | Aging |
| Volume | 8 |
| Issue number | 4 |
| Early online date | 23 Feb 2016 |
| DOIs | |
| Publication status | Published - Apr 2016 |
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Keywords
- calorie restriction
- circadian rhythm
- hunger
- Hypothalamus
- transcriptomics
Cite this
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. / Derous, Davina; Mitchell, Sharon E.; Green, Cara L.; Chen, Luonan; Han, Jing-Dong J.; Wang, Yingchun; Promislow, Daniel E. L.; Lusseau, David; Speakman, John R. (Corresponding Author); Douglas, Alex (Corresponding Author).
In: Aging, Vol. 8, No. 4, 04.2016, p. 642-661.Research output: Contribution to journal › Article
}
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
SP - 642
EP - 661
JO - Aging
JF - Aging
SN - 1945-4589
IS - 4
ER -