PMID- 36642218
OWN - NLM
STAT- MEDLINE
DCOM- 20230207
LR  - 20231127
IS  - 2212-8778 (Electronic)
IS  - 2212-8778 (Linking)
VI  - 68
DP  - 2023 Feb
TI  - Intrinsic cardiorespiratory fitness modulates clinical and molecular response to 
      caloric restriction.
PG  - 101668
LID - S2212-8778(23)00002-9 [pii]
LID - 10.1016/j.molmet.2023.101668 [doi]
LID - 101668
AB  - OBJECTIVE: Caloric restriction (CR) is one extrinsic intervention that can 
      improve metabolic health, and it shares many phenotypical parallels with 
      intrinsic high cardiorespiratory fitness (CRF), including reduced adiposity, 
      increased cardiometabolic health, and increased longevity. CRF is a highly 
      heritable trait in humans and has been established in a genetic rat model 
      selectively bred for high (HCR) and low (LCR) CRF, in which the HCR live longer 
      and have reduced body weight compared to LCR. This study addresses whether the 
      inherited high CRF phenotype occurs through similar mechanisms by which CR 
      promotes health and longevity. METHODS: We compared HCR and LCR male rats fed ad 
      libitum (AL) or calorically restricted (CR) for multiple physiological, 
      metabolic, and molecular traits, including running capacity at 2, 8, and 12 
      months; per-hour metabolic cage activity over daily cycles at 6 and 12 months; 
      and plasma lipidomics, liver and muscle transcriptomics, and body composition 
      after 12 months of treatment. RESULTS: LCR-CR developed a physiological profile 
      that mirrors the high-CRF phenotype in HCR-AL, including reduced adiposity and 
      increased insulin sensitivity. HCR show higher spontaneous activity than LCR. 
      Temporal modeling of hourly energy expenditure (EE) dynamics during the day, 
      adjusted for body weight and hourly activity levels, suggest that CR has an 
      EE-suppressing effect, and high-CRF has an EE-enhancing effect. Pathway analysis 
      of gene transcripts indicates that HCR and LCR both show a response to CR that is 
      similar in the muscle and different in the liver. CONCLUSIONS: CR provides LCR a 
      health-associated positive effect on physiological parameters that strongly 
      resemble HCR. Analysis of whole-body EE and transcriptomics suggests that HCR and 
      LCR show line-dependent responses to CR that may be accreditable to difference in 
      genetic makeup. The results do not preclude the possibility that CRF and CR 
      pathways may converge.
CI  - Copyright (c) 2023 The Author(s). Published by Elsevier GmbH.. All rights reserved.
FAU - Fleischman, Johanna Y
AU  - Fleischman JY
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA.
FAU - Qi, Nathan R
AU  - Qi NR
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA; Department of Internal Medicine, University of Michigan, Ann 
      Arbor, MI, USA; Michigan Mouse Metabolic Phenotyping Center, University of 
      Michigan, Ann Arbor, MI, USA.
FAU - Treutelaar, Mary K
AU  - Treutelaar MK
AD  - Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA.
FAU - Britton, Steven L
AU  - Britton SL
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA; Department of Anesthesiology, University of Michigan, Ann Arbor, 
      MI, USA.
FAU - Koch, Lauren G
AU  - Koch LG
AD  - Department of Physiology and Pharmacology, The University of Toledo, Toledo, OH, 
      USA.
FAU - Li, Jun Z
AU  - Li JZ
AD  - Department of Human Genetics, University of Michigan, Ann Arbor, MI, USA; 
      Department of Computational Medicine and Bioinformatics, University of Michigan, 
      Ann Arbor, MI, USA.
FAU - Burant, Charles F
AU  - Burant CF
AD  - Department of Molecular and Integrative Physiology, University of Michigan, Ann 
      Arbor, MI, USA; Department of Internal Medicine, University of Michigan, Ann 
      Arbor, MI, USA. Electronic address: burantc@med.umich.edu.
LA  - eng
GR  - F31 DK130253/DK/NIDDK NIH HHS/United States
GR  - P30 DK089503/DK/NIDDK NIH HHS/United States
GR  - P30 DK020572/DK/NIDDK NIH HHS/United States
GR  - R01 DK099034/DK/NIDDK NIH HHS/United States
GR  - U2C DK110768/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20230112
PL  - Germany
TA  - Mol Metab
JT  - Molecular metabolism
JID - 101605730
SB  - IM
MH  - Humans
MH  - Rats
MH  - Male
MH  - Animals
MH  - *Cardiorespiratory Fitness
MH  - Caloric Restriction
MH  - *Running/physiology
MH  - Obesity/metabolism
MH  - Body Weight
PMC - PMC9938335
OTO - NOTNLM
OT  - Caloric restriction
OT  - Cardiorespiratory fitness
OT  - Metabolism
OT  - Mitochondria
OT  - Muscle
COIS- Conflict of interest None declared.
EDAT- 2023/01/16 06:00
MHDA- 2023/02/08 06:00
PMCR- 2023/01/12
CRDT- 2023/01/15 19:25
PHST- 2022/10/25 00:00 [received]
PHST- 2022/12/21 00:00 [revised]
PHST- 2023/01/05 00:00 [accepted]
PHST- 2023/01/16 06:00 [pubmed]
PHST- 2023/02/08 06:00 [medline]
PHST- 2023/01/15 19:25 [entrez]
PHST- 2023/01/12 00:00 [pmc-release]
AID - S2212-8778(23)00002-9 [pii]
AID - 101668 [pii]
AID - 10.1016/j.molmet.2023.101668 [doi]
PST - ppublish
SO  - Mol Metab. 2023 Feb;68:101668. doi: 10.1016/j.molmet.2023.101668. Epub 2023 Jan 
      12.