PMID- 37096321
OWN - NLM
STAT- MEDLINE
DCOM- 20230511
LR  - 20230523
IS  - 2050-084X (Electronic)
IS  - 2050-084X (Linking)
VI  - 12
DP  - 2023 Apr 25
TI  - The effects of caloric restriction on adipose tissue and metabolic health are 
      sex- and age-dependent.
LID - 10.7554/eLife.88080 [doi]
LID - e88080
AB  - Caloric restriction (CR) reduces the risk of age-related diseases in numerous 
      species, including humans. CR's metabolic effects, including decreased adiposity 
      and improved insulin sensitivity, are important for its broader health benefits; 
      however, the extent and basis of sex differences in CR's health benefits are 
      unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass 
      and improved glucose tolerance and insulin sensitivity, whereas these effects 
      were blunted or absent in young females. Females' resistance to fat loss was 
      associated with decreased lipolysis, energy expenditure and fatty acid oxidation, 
      and increased postprandial lipogenesis, compared to males. The sex differences in 
      glucose homeostasis were not associated with differential glucose uptake but with 
      altered hepatic ceramide content and substrate metabolism: compared to CR males, 
      CR females had lower TCA cycle activity and higher blood ketone concentrations, a 
      marker of hepatic acetyl-CoA content. This suggests that males use hepatic 
      acetyl-CoA for the TCA cycle whereas in females it accumulates, stimulating 
      gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months 
      old), when females are anoestrus, CR decreased fat mass and improved glucose 
      homeostasis similarly in both sexes. Finally, in a cohort of overweight and obese 
      humans, CR-induced fat loss was also sex- and age-dependent: younger females (<45 
      years) resisted fat loss compared to younger males while in older subjects (>45 
      years) this sex difference was absent. Collectively, these studies identify 
      age-dependent sex differences in the metabolic effects of CR and highlight 
      adipose tissue, the liver and oestrogen as key determinants of CR's metabolic 
      benefits. These findings have important implications for understanding the 
      interplay between diet and health, and for maximising the benefits of CR in 
      humans.
CI  - (c) 2023, Suchacki, Thomas, Ikushima et al.
FAU - Suchacki, Karla J
AU  - Suchacki KJ
AUID- ORCID: 0000-0002-4688-4126
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Thomas, Benjamin J
AU  - Thomas BJ
AUID- ORCID: 0000-0001-8344-5256
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Ikushima, Yoshiko M
AU  - Ikushima YM
AUID- ORCID: 0000-0002-9987-874X
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Chen, Kuan-Chan
AU  - Chen KC
AUID- ORCID: 0000-0001-7653-6491
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
AD  - Division of Endocrinology and Metabolism, Department of Internal Medicine, 
      Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan.
FAU - Fyfe, Claire
AU  - Fyfe C
AUID- ORCID: 0000-0001-6521-2651
AD  - Rowett Institute, University of Aberdeen, Aberdeen, United Kingdom.
FAU - Tavares, Adriana A S
AU  - Tavares AAS
AUID- ORCID: 0000-0001-7505-9144
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
AD  - Edinburgh Imaging, University of Edinburgh, The Queen's Medical Research 
      Institute, Edinburgh BioQuarter, Edinburgh, United Kingdom.
FAU - Sulston, Richard J
AU  - Sulston RJ
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Lovdel, Andrea
AU  - Lovdel A
AUID- ORCID: 0000-0002-4262-8491
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Woodward, Holly J
AU  - Woodward HJ
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Han, Xuan
AU  - Han X
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Mattiucci, Domenico
AU  - Mattiucci D
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Brain, Eleanor J
AU  - Brain EJ
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Alcaide-Corral, Carlos J
AU  - Alcaide-Corral CJ
AUID- ORCID: 0000-0002-3002-0649
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
AD  - Edinburgh Imaging, University of Edinburgh, The Queen's Medical Research 
      Institute, Edinburgh BioQuarter, Edinburgh, United Kingdom.
FAU - Kobayashi, Hiroshi
AU  - Kobayashi H
AUID- ORCID: 0000-0002-0924-1252
AD  - Department of Stem Cell Biology, Research Institute, National Center for Global 
      Health and Medicine, Tokyo, Japan.
FAU - Gray, Gillian A
AU  - Gray GA
AUID- ORCID: 0000-0003-3104-3305
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Whitfield, Phillip D
AU  - Whitfield PD
AUID- ORCID: 0000-0002-0814-4119
AD  - Division of Biomedical Sciences, University of the Highlands and Islands, Centre 
      for Health Sciences, Inverness, United Kingdom.
AD  - Institute of Infection, Immunity & Inflammation, University of Glasgow, Glasgow, 
      United Kingdom.
FAU - Stimson, Roland H
AU  - Stimson RH
AUID- ORCID: 0000-0002-9002-6188
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Morton, Nicholas M
AU  - Morton NM
AUID- ORCID: 0000-0001-8218-8462
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
FAU - Johnstone, Alexandra M
AU  - Johnstone AM
AUID- ORCID: 0000-0002-5484-292X
AD  - Rowett Institute, University of Aberdeen, Aberdeen, United Kingdom.
FAU - Cawthorn, William P
AU  - Cawthorn WP
AUID- ORCID: 0000-0001-7832-5057
AD  - University/BHF Centre for Cardiovascular Science, University of Edinburgh, The 
      Queen's Medical Research Institute, Edinburgh BioQuarter, Edinburgh, United 
      Kingdom.
LA  - eng
SI  - GEO/GSE230402
GR  - MR/M021394/1/MRC_/Medical Research Council/United Kingdom
GR  - RG/16/10/32375/BHF_/British Heart Foundation/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20230425
PL  - England
TA  - Elife
JT  - eLife
JID - 101579614
RN  - 72-89-9 (Acetyl Coenzyme A)
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
UOF - doi: 10.1101/2022.02.20.481222
MH  - Humans
MH  - Male
MH  - Female
MH  - Mice
MH  - Animals
MH  - Aged
MH  - Middle Aged
MH  - Infant
MH  - *Caloric Restriction
MH  - *Insulin Resistance
MH  - Weight Loss
MH  - Acetyl Coenzyme A
MH  - Adipose Tissue/metabolism
MH  - Obesity
MH  - Glucose/metabolism
PMC - PMC10171869
OTO - NOTNLM
OT  - adipose tissue
OT  - caloric restriction
OT  - glucose homeostasis
OT  - healthy ageing
OT  - human
OT  - insulin sensitivity
OT  - medicine
OT  - mouse
OT  - sex differences
COIS- KS, BT, YI, KC, CF, AT, RS, AL, HW, XH, DM, EB, CA, HK, GG, PW, RS, NM, AJ, WC No 
      competing interests declared
EDAT- 2023/04/25 06:42
MHDA- 2023/05/11 06:42
PMCR- 2023/04/25
CRDT- 2023/04/25 02:52
PHST- 2023/03/24 00:00 [received]
PHST- 2023/03/26 00:00 [accepted]
PHST- 2023/05/11 06:42 [medline]
PHST- 2023/04/25 06:42 [pubmed]
PHST- 2023/04/25 02:52 [entrez]
PHST- 2023/04/25 00:00 [pmc-release]
AID - 88080 [pii]
AID - 10.7554/eLife.88080 [doi]
PST - epublish
SO  - Elife. 2023 Apr 25;12:e88080. doi: 10.7554/eLife.88080.