Strain-specific metabolic responses to long-term caloric restriction in female ILSXISS recombinant inbred mice

Mulvey, L., Wilkie, S. E., Griffiths, K., Sinclair, A., McGuinness, D., Watson, D. G. and Selman, C. (2021) Strain-specific metabolic responses to long-term caloric restriction in female ILSXISS recombinant inbred mice. Molecular and Cellular Endocrinology, 535, 111376. (doi: 10.1016/j.mce.2021.111376) (PMID:34246728)

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Abstract

The role that genetic background may play in the responsiveness of organisms to interventions such as caloric restriction (CR) is underappreciated but potentially important. We investigated genetic background on a suite of metabolic parameters in female recombinant inbred ILSXISS mouse strains previously reported to show divergent lifespan responses to 40% CR (TejJ89-lifespan extension; TejJ48-lifespan unaffected; TejJ114-lifespan shortening). Body mass was reduced across all strains following 10 months of 40% CR, although this loss (relative to ad libitum controls) was greater in TejJ114 relative to the other strains. Gonadal white adipose tissue (gWAT) mass was similarly reduced across all strains following 40% CR, but brown adipose tissue (BAT) mass increased only in strains TejJ89 and TejJ48. Surprisingly, glucose tolerance was improved by CR only in TejJ114, while strains TejJ89 and TejJ114 were relatively hyperinsulinemic following CR relative to their AL controls. We subsequently undertook an unbiased metabolomic approach in gWAT and BAT tissue from strains TejJ89 and TejJ114 mice under AL and 40% CR. gWAT from TejJ89 showed a significant reduction in several long chain unsaturated fatty acids following 40% CR, but gWAT from TejJ114 appeared relatively unresponsive to CR, with far fewer metabolites changing. Phosphatidylethanoloamine lipids within the BAT were typically elevated in TejJ89 following CR, while some phosphatidylglycerol lipids were decreased. However, BAT from strain TejJ114 again appeared unresponsive to CR. These data highlight strain-specific metabolic differences exist in ILSXISS mice following CR. We suggest that precisely how different fat depots respond dynamically to CR may be an important factor in the variable longevity under CR observed in these mice.

Item Type:Articles
Additional Information:This research (and PhD funding to LM) was supported, in part, from start-up funds from the University of Glasgow (College of Medical, Veterinary and Life Sciences), a MRC Precision Medicine Doctoral Training Program PhD studentship (to SEW; Ref: MR/N013166/1) and BBSRC funding (BB/S014330/1).
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Mulvey, Lorna and Selman, Professor Colin and Wilkie, Stephen and Griffiths, Mrs Kate and Sinclair, Miss Amy
Authors: Mulvey, L., Wilkie, S. E., Griffiths, K., Sinclair, A., McGuinness, D., Watson, D. G., and Selman, C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Biodiversity Animal Health and Comparative Medicine
Journal Name:Molecular and Cellular Endocrinology
Publisher:Elsevier
ISSN:0303-7207
ISSN (Online):1872-8057
Published Online:09 July 2021
Copyright Holders:Copyright © 2021 The Authors
First Published:First published in Molecular and Cellular Endocrinology 535: 111376
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
304008MRC Flexible SupplementMorven BarlassMedical Research Council (MRC)MR/N013166/1CAMS - Cardiovascular Science
305154Consolidating the role of RNA polymerase III in healthy ageing: from worms to flies to miceColin SelmanBiotechnology and Biological Sciences Research Council (BBSRC)BB/S014330/1Institute of Biodiversity, Animal Health and Comparative Medicine