Increased TCA cycle intermediates in response to diet with Deanna protocol in ALS mouse model (578.3)

Abstract

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting motor neurons and is characterized by progressive muscle weakness, paralysis, and, eventually, death. There is no cure for ALS. This metabolic profiling study was conducted to determine the metabolic impacts of a multi‐component experimental nutritional regimen known as the Deanna Protocol (DP) to gain insights into possible mechanisms by which this diet is reported to help slow the progression of ALS.In this 30 sample study SOD1 G93A mice were fed for 6 weeks a standard diet (CTRL) or diets representing a low (12%) or high (22%) dose of DP. Comparison of the plasma global biochemical profiles were performed at endpoint by Metabolon that revealed key metabolic differences.The DP diet dose‐dependently increased compounds associated with glycolysis and the tricarboxylic acid (TCA) cycle. Alpha‐ketoglutarate, a key ingredient of DP, pyruvate, lactate succinate, fumarate, malate and phosphatidylcholine (PC) metabolites were elevated in the high DP group relative to the CTRL. Elevations of intermediates of fatty acid oxidation (FAO) and ready FAO substrates indicated a likely increased beta‐oxidation in response to the DP diet.Substantial build‐up of TCA cycle components combined with acetyl‐CoA provided by increased beta‐oxidation, likely led to greater mitochondrial ATP production, which might be the reason of improved motor function and slower progression of disease.Grant Funding Source: Winning the Fight Foundation