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Ketogenic Diet Modulates NAD

Marwa Elamin1, David N Ruskin2, Susan A Masino2

  • 1Graduate Program in Neuroscience, Department of Biology, University of Hartford, West Hartford, CT, United States.

Frontiers in Cellular Neuroscience
|September 15, 2018
PubMed
Summary
This summary is machine-generated.

The ketogenic diet (KD) rapidly boosts brain NAD+ levels, enhancing sirtuin enzymes and DNA repair. This mechanism may explain KD

Keywords:
PARP-1hippocampusketone bodieslongevitymetabolismnicotinamide adenine dinucleotideoxidative stresssirtuin

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Area of Science:

  • Neuroscience
  • Metabolic Science
  • Molecular Biology

Background:

  • The ketogenic diet (KD) shows promise for neurological disorders beyond epilepsy.
  • A fundamental mechanism for KD's broad therapeutic effects is currently unknown.
  • Previous research indicated KD increases hippocampal nicotinamide adenine dinucleotide+ (NAD+) in rats.

Purpose of the Study:

  • To investigate the impact of KD on NAD+-dependent enzymes and DNA damage markers in the rat hippocampus.
  • To explore the rapid and persistent effects of KD on cellular resilience pathways.

Main Methods:

  • Rats were fed either regular chow or a KD for 2 days or 3 weeks.
  • Quantification of hippocampal sirtuin enzyme activity, Sirt1 mRNA, poly-ADP ribose polymerase-1 (PARP-1), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels.

Main Results:

  • KD induced a rapid and sustained increase in nuclear sirtuin activity and Sirt1 mRNA levels.
  • PARP-1 and 8-OHdG levels, a marker of oxidative DNA damage, significantly decreased after KD treatment.
  • These changes occurred within 2 days and persisted for 3 weeks.

Conclusions:

  • The ketogenic diet rapidly modulates brain energy metabolism via NAD+-dependent pathways.
  • KD enhances cellular resilience against DNA damage through NAD+-related mechanisms.
  • This study provides a mechanistic link between KD, NAD+ metabolism, and potential benefits for various neurological conditions and overall healthspan.