The Effects of Graded Levels of Calorie Restriction: X. Transcriptomic Responses of Epididymal Adipose Tissue

Davina Derous; Sharon E Mitchell; Cara L Green; Yingchun Wang; Jing Dong J Han; Luonan Chen; Daniel E L Promislow; David Lusseau; Alex Douglas; John R Speakman

doi:10.1093/gerona/glx101

The Effects of Graded Levels of Calorie Restriction: X. Transcriptomic Responses of Epididymal Adipose Tissue

Davina Derous, Sharon E Mitchell, Cara L Green, Yingchun Wang, Jing Dong J Han, Luonan Chen, Daniel E L Promislow, David Lusseau, Alex Douglas, John R Speakman

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Abstract

Calorie restriction (CR) leads to a remarkable decrease in adipose tissue mass and increases longevity in many taxa. Since the discovery of leptin, the secretory abilities of adipose tissue have gained prominence in the responses to CR. We quantified transcripts of epididymal white adipose tissue of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months. The numbers of differentially expressed genes (DEGs) involved in NF-κB, HIF1-α and p53 signalling increased with increasing levels of CR. These pathways were all significantly downregulated at 40% CR relative to 12h ad libitum feeding. In addition, graded CR had a substantial impact on DEGs associated with pathways involved in angiogenesis. Of the 497 genes differentially expressed with graded CR, 155 of these genes included a signal peptide motif. These putative signalling proteins were involved in the response to ketones, TGF-β signalling, negative regulation of insulin secretion and inflammation. This accords with the previously established effects of graded CR on glucose homeostasis in the same mice. Overall these data suggest reduced levels of adipose tissue under CR may contribute to the protective impact of CR in multiple ways linked to changes in a large population of secreted proteins.

Original language	English
Pages (from-to)	279-288
Number of pages	10
Journal	The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Volume	73
Issue number	3
Early online date	27 May 2017
DOIs	https://doi.org/10.1093/gerona/glx101
Publication status	Published - 2 Mar 2018

Keywords

biology of ageing
genetics
signalling

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10.1093/gerona/glx101Licence: CC BY

The Effects of Graded Levels of Calorie Restriction
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.
Final published version, 17.2 MBLicence: CC BY

Davina Derous
- Biological Sciences, Aberdeen Centre For Environmental Sustainability - Lecturer
Person: Academic

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Derous, D., Mitchell, S. E., Green, C. L., Wang, Y., Han, J. D. J., Chen, L., Promislow, D. E. L., Lusseau, D., Douglas, A., & Speakman, J. R. (2018). The Effects of Graded Levels of Calorie Restriction: X. Transcriptomic Responses of Epididymal Adipose Tissue. The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, 73(3), 279-288. https://doi.org/10.1093/gerona/glx101

Derous, D , Mitchell, SE, Green, CL, Wang, Y, Han, JDJ, Chen, L, Promislow, DEL, Lusseau, D , Douglas, A & Speakman, JR 2018, 'The Effects of Graded Levels of Calorie Restriction: X. Transcriptomic Responses of Epididymal Adipose Tissue', The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences, vol. 73, no. 3, pp. 279-288. https://doi.org/10.1093/gerona/glx101

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abstract = "Calorie restriction (CR) leads to a remarkable decrease in adipose tissue mass and increases longevity in many taxa. Since the discovery of leptin, the secretory abilities of adipose tissue have gained prominence in the responses to CR. We quantified transcripts of epididymal white adipose tissue of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months. The numbers of differentially expressed genes (DEGs) involved in NF-κB, HIF1-α and p53 signalling increased with increasing levels of CR. These pathways were all significantly downregulated at 40% CR relative to 12h ad libitum feeding. In addition, graded CR had a substantial impact on DEGs associated with pathways involved in angiogenesis. Of the 497 genes differentially expressed with graded CR, 155 of these genes included a signal peptide motif. These putative signalling proteins were involved in the response to ketones, TGF-β signalling, negative regulation of insulin secretion and inflammation. This accords with the previously established effects of graded CR on glucose homeostasis in the same mice. Overall these data suggest reduced levels of adipose tissue under CR may contribute to the protective impact of CR in multiple ways linked to changes in a large population of secreted proteins. ",

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N2 - Calorie restriction (CR) leads to a remarkable decrease in adipose tissue mass and increases longevity in many taxa. Since the discovery of leptin, the secretory abilities of adipose tissue have gained prominence in the responses to CR. We quantified transcripts of epididymal white adipose tissue of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months. The numbers of differentially expressed genes (DEGs) involved in NF-κB, HIF1-α and p53 signalling increased with increasing levels of CR. These pathways were all significantly downregulated at 40% CR relative to 12h ad libitum feeding. In addition, graded CR had a substantial impact on DEGs associated with pathways involved in angiogenesis. Of the 497 genes differentially expressed with graded CR, 155 of these genes included a signal peptide motif. These putative signalling proteins were involved in the response to ketones, TGF-β signalling, negative regulation of insulin secretion and inflammation. This accords with the previously established effects of graded CR on glucose homeostasis in the same mice. Overall these data suggest reduced levels of adipose tissue under CR may contribute to the protective impact of CR in multiple ways linked to changes in a large population of secreted proteins.

AB - Calorie restriction (CR) leads to a remarkable decrease in adipose tissue mass and increases longevity in many taxa. Since the discovery of leptin, the secretory abilities of adipose tissue have gained prominence in the responses to CR. We quantified transcripts of epididymal white adipose tissue of male C57BL/6 mice exposed to graded levels of CR (0% to 40% CR) for three months. The numbers of differentially expressed genes (DEGs) involved in NF-κB, HIF1-α and p53 signalling increased with increasing levels of CR. These pathways were all significantly downregulated at 40% CR relative to 12h ad libitum feeding. In addition, graded CR had a substantial impact on DEGs associated with pathways involved in angiogenesis. Of the 497 genes differentially expressed with graded CR, 155 of these genes included a signal peptide motif. These putative signalling proteins were involved in the response to ketones, TGF-β signalling, negative regulation of insulin secretion and inflammation. This accords with the previously established effects of graded CR on glucose homeostasis in the same mice. Overall these data suggest reduced levels of adipose tissue under CR may contribute to the protective impact of CR in multiple ways linked to changes in a large population of secreted proteins.

KW - biology of ageing

KW - genetics

KW - signalling

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The Effects of Graded Levels of Calorie Restriction: X. Transcriptomic Responses of Epididymal Adipose Tissue

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Davina Derous

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