Brain NAD Is Associated With ATP Energy Production and Membrane Phospholipid Turnover in Humans

Abstract

The brain requires a large amount of energy, mostly derived from the metabolism of glucose, which decreases substantially with age and neurological diseases. While mounting evidence in model organisms illustrates the central role of brain nicotinamide adenine dinucleotide (NAD) for maintaining energy homeostasis, similar data are sparse in humans. This study explores the correlations between brain NAD, energy production and membrane phospholipid metabolism by 31-phosphorous magnetic resonance spectroscopy (31P-MRS) across 50 healthy participants including a young (mean age 27.1-year-old) and middle-aged (mean age 56.4-year-old) group. The analysis revealed that brain NAD level and NAD+/NADH redox ratio were positively associated with ATP level and the rate of energy production, respectively. Moreover, a metabolic network linking NAD with membrane phospholipid metabolism, energy production, and aging was identified. An inverted trend between age and NAD level was detected. These results pave the way for the use of 31P-MRS as a powerful non-invasive tool to support the development of new therapeutic interventions targeting NAD associated phospho-metabolic pathways in brain aging and neurological diseases.

Neuroprotective effect of sodium alginate against chromium-induced brain damage in rats

“…In the present study, the significant decline detected in the NAD + levels in the brain tissues of Cr-intoxicated group confirmed the occurrence of brain injury in this group. This infers that Cr(VI) induced toxicity via inhibiting the mitochondrial dehydrogenases activity such as NADH dehydrogenase, which in turn causes depletion of NADH pool from the tissues [ 56 ]. Consistently, previous study postulated the neurotoxicity in the chicken brains following exposure to Cr(VI) [ 19 ].…”

Effects of Acute and Chronic Resistance Exercise on the Skeletal Muscle Metabolome

“…In metabolically active tissues the levels of NAD + /NADH and nucleotides are tightly linked to each other and ensure high rates of ATP turnover. [54] Hence, it is comprehensible that we observed changes in metabolites related to nucleotide and NADH turnover also in skeletal muscle. Increased ATP breakdown due to EE but also RE, exerts a rise in adenine nucleotide metabolites.…”

Down-regulation of EPB41L4A-AS1 mediated the brain aging and neurodegenerative diseases via damaging synthesis of NAD+ and ATP

“…Previous studies have reported that brain NAD + was associated with ATP synthesis and membrane phospholipid turnover in humans [ 28 ], while ATP played a very important role in the normal brain [ 29 ]. Furthermore, NAD + has been strongly associated with aging and neurodegenerative diseases [ 18 , 30 ], with evidence suggesting NAD + can inhibit Alzheimer's disease [ 31 ].…”

“…An increasing body of evidence suggests that brain NAD + levels play a central role in maintaining energy homeostasis and ATP production [ 28 ]. In this study, we found that the aging-induced down-regulation of EPB41L4A-AS1 not only disturbed NAD + biosynthesis but also affected ATP production.…”

“…In this study, we found that the aging-induced down-regulation of EPB41L4A-AS1 not only disturbed NAD + biosynthesis but also affected ATP production. It has been established that NAD + accepts hydride equivalents, forming NADH, providing electrons to the electron transport chain to generate ATP [ 28 ]. In this respect, a decrease of NAD + could disrupt the process and impact ATP synthesis.…”