The Effects of Graded Levels of Calorie Restriction: XIV. Global Metabolomics Screen Reveals Brown Adipose Tissue Changes in Amino Acids, Catecholamines, and Antioxidants After Short-Term Restriction in C57BL/6 Mice

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

13 Citations (Scopus)
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Abstract

Animals undergoing calorie restriction (CR) often lower their body temperature to conserve energy. Brown adipose tissue (BAT) is stimulated through norepinephrine when rapid heat production is needed, as it is highly metabolically active due to the uncoupling of the electron transport chain from ATP synthesis. To better understand how BAT metabolism changes with CR, we used metabolomics to identify 883 metabolites that were significantly differentially expressed in the BAT of C57BL/6 mice, fed graded CR (10%, 20%, 30%, and 40% CR relative to their individual baseline intake), compared with mice fed ad libitum (AL) for 12 hours a day. Pathway analysis revealed that graded CR had an impact on the TCA cycle and fatty acid degradation. In addition, an increase in nucleic acids and catecholamine pathways was seen with graded CR in the BAT metabolome. We saw increases in antioxidants with CR, suggesting a beneficial effect of mitochondrial uncoupling. Importantly, the instigator of BAT activation, norepinephrine, was increased with CR, whereas its precursors L-tyrosine and dopamine were decreased, indicating a shift of metabolites through the activation pathway. Several of these key changes were correlated with food anticipatory activity and body temperature, indicating BAT activation may be driven by responses to hunger.

Original languageEnglish
Pages (from-to)218-229
Number of pages12
JournalThe Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
Volume75
Issue number2
Early online date9 Apr 2019
DOIs
Publication statusPublished - Feb 2020

Bibliographical note

The work was supported by the UK Biotechnology and Biological Sciences Research Council BBSRC (BB/G009953/1 and BB/J020028/1 to JRS) and a studentship of CLG from the BBSRC EastBio Doctoral Training Partnership. CLG received support from the lab of DP; DP was supported in part by NIH grant AGO49494. The authors declare no conflicts of interests.

Data Availability Statement

Supplementary data are available at The Journals of Gerontology, Series A: Biological Sciences and Medical Sciences online.

Keywords

  • thermogenesis
  • diabetes
  • dopamine
  • torpor
  • obesity
  • Obesity
  • Dopamine
  • Thermogenesis
  • Torpor
  • Diabetes

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