PMID- 31249833
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 2296-861X (Print)
IS  - 2296-861X (Electronic)
IS  - 2296-861X (Linking)
VI  - 6
DP  - 2019
TI  - Caloric Restriction Alters Postprandial Responses of Essential Brain Metabolites 
      in Young Adult Mice.
PG  - 90
LID - 10.3389/fnut.2019.00090 [doi]
LID - 90
AB  - Caloric restriction (CR) has been shown to extend longevity and protect brain 
      function in aging. However, the effects of CR in young adult mice remain largely 
      unexplored. In addition to the fundamental, long-term changes, recent studies 
      demonstrate that CR has a significant impact on transient, postprandial metabolic 
      flexibility and turnover compared to control groups. The goal of this study was 
      to identify the brain metabolic changes at a transient (2 h) and steady (6 h) 
      postprandial state in young mice (5-6 months of age) fed with CR or ad libitum 
      (AL; free eating). Using metabolomics profiling, we show that CR mice had 
      significantly higher levels of neurotransmitters (e.g., glutamate, 
      N-acetylglutamate), neuronal integrity markers (e.g., NAA and NAAG), essential 
      fatty acids (e.g., DHA and DPA), and biochemicals associated carnitine metabolism 
      (related to reduced oxidative stress and inflammation) in the cerebral cortex and 
      hippocampus at 2-h. These biochemicals remained at high levels at the 6-h 
      postprandial time-point. The AL mice did not show the similar increases in 
      essential fatty acid and carnitine metabolism until the 6-h time-point, and 
      failed to show increases in neurotransmitters and neuronal integrity markers at 
      any time-point. On the other hand, metabolites related to glucose 
      utilization-glycolysis and pentose phosphate pathway (PPP)-were low in the CR 
      mice throughout the 6-h period and significantly increased at the 6-h time-point 
      in the AL mice. Our findings suggest that CR induces distinct postprandial 
      responses in metabolites that are essential to maintain brain functions. CR mice 
      produced higher levels of essential brain metabolites in a shorter period after a 
      meal and sustained the levels for an extended period, while maintaining a lower 
      level of glucose utilization. These early brain metabolism changes in the CR mice 
      might play a critical role for neuroprotection in aging. Understanding the 
      interplay between dietary intervention and postprandial metabolic responses from 
      an early age may have profound implications for impeding brain aging and reducing 
      risk for neurodegenerative disorders.
FAU - Yanckello, Lucille M
AU  - Yanckello LM
AD  - Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United 
      States.
AD  - Department of Pharmacology and Nutritional Science, University of Kentucky, 
      Lexington, KY, United States.
FAU - Young, Lyndsay E A
AU  - Young LEA
AD  - Department of Molecular and Cellular Biochemistry, University of Kentucky, 
      Lexington, KY, United States.
FAU - Hoffman, Jared D
AU  - Hoffman JD
AD  - Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United 
      States.
FAU - Mohney, Robert P
AU  - Mohney RP
AD  - Metabolon Inc., Durham, NC, United States.
FAU - Keaton, Mignon A
AU  - Keaton MA
AD  - Metabolon Inc., Durham, NC, United States.
FAU - Abner, Erin
AU  - Abner E
AD  - Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United 
      States.
AD  - Department of Epidemiology, University of Kentucky, Lexington, KY, United States.
FAU - Lin, Ai-Ling
AU  - Lin AL
AD  - Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, United 
      States.
AD  - Department of Pharmacology and Nutritional Science, University of Kentucky, 
      Lexington, KY, United States.
AD  - F. Joseph Halcomb III, M. D. Department of Biomedical Engineering, University of 
      Kentucky, Lexington, KY, United States.
AD  - Department of Neuroscience, University of Kentucky, Lexington, KY, United States.
LA  - eng
GR  - T32 DK007778/DK/NIDDK NIH HHS/United States
PT  - Journal Article
DEP - 20190612
PL  - Switzerland
TA  - Front Nutr
JT  - Frontiers in nutrition
JID - 101642264
PMC - PMC6582370
OTO - NOTNLM
OT  - aging
OT  - caloric restriction
OT  - metabolic plasticity
OT  - metabolomics
OT  - neurodegeneration
OT  - neurotransmitters
OT  - postprandial brain metabolism
EDAT- 2019/06/30 06:00
MHDA- 2019/06/30 06:01
PMCR- 2019/01/01
CRDT- 2019/06/29 06:00
PHST- 2018/12/21 00:00 [received]
PHST- 2019/05/24 00:00 [accepted]
PHST- 2019/06/29 06:00 [entrez]
PHST- 2019/06/30 06:00 [pubmed]
PHST- 2019/06/30 06:01 [medline]
PHST- 2019/01/01 00:00 [pmc-release]
AID - 10.3389/fnut.2019.00090 [doi]
PST - epublish
SO  - Front Nutr. 2019 Jun 12;6:90. doi: 10.3389/fnut.2019.00090. eCollection 2019.