Experimental evidence on the efficacy of two new metabolic modulators on mitochondrial biogenesis and function in mouse cardiomyocytes

Abstract

Proper maintenance of mitochondrial homeostasis is essential for cell health, and mitochondrial dysfunction underlies several metabolic and heart diseases. Stimulation of mitochondrial biogenesis represents a valuable therapeutic tool for the prevention and treatment of disorders characterized by a deficit in energy metabolism. The present study aimed to potentiate the mitochondrial biogenetic efficacy of an amino acid (AA) mixture, enriched in branched-chain amino acids (BCAAs), which we previously showed to boost mitochondrial biogenesis, leading to life span extension and reducing of muscle and liver damage. Hence, we designed and studied several innovative mixtures. Here, we report on two new AA formulas, ?5 and E7, created on the BCAA-enriched amino acid mixture (BCAAem) template and enriched with Krebs cycle substrates, including succinate, malate, and citrate. Cardiomyocytes in culture exposed to either mixture showed increased mitochondrial DNA amount, mitochondrial biogenesis markers, and oxygen consump-tion. Furthermore, ?5 and E7 also increased the expression of BCAA catabolic genes. Most importantly, all of these effects of ?5 and E7 were more pronounced than those observed with BCAAem, confirming the higher mitochondrial biogenesis potential of these new formulas. Therefore, ?5 and E7 could represent a more efficient tool for the nutritional treatment of diseases in which energy production is defective.