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 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 |
Bibliographical note
AcknowledgementsWe 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).
Keywords
- calorie restriction
- circadian rhythm
- hunger
- Hypothalamus
- transcriptomics
Fingerprint
Dive into the research topics of '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'. Together they form a unique fingerprint.Profiles
Equipment
-
Centre for Genome-Enabled Biology and Medicine
Elaina Susan Renata Collie-Duguid (Manager)
School of Medicine, Medical Sciences & NutritionResearch Facilities: Facility