Branched chain amino acids, an ''essential'' link between diet, clock and sleep?

Abstract

The branched-chain amino acids: leucine, isoleucine and valine occupy a special place among the essential amino acids because of their importance not only in the structure of proteins but also in general and cerebral metabolism. Among the first amino acids absorbed after food intake, they play a major role in the regulation of protein synthesis and insulin secretion. They are involved in the modulation of brain uptake of monoamine precursors with which they may compete for occupancy of a common transporter. In the brain, branched-chain amino acids are involved not only in protein synthesis but also in the metabolic cycles of GABA and Glutamate, and in energy metabolism. In particular, they can affect GABAergic neurons and the excitation/inhibition balance. Branched-chain amino acids are known for the 24-hour rhythmicity of their plasma concentrations, which is remarkably conserved in rodent models. This rhythmicity is partly circadian, independent of sleep and food. Moreover, their concentration increases when sleep is disturbed and in obesity and diabetes. The mechanisms regulating these rhythms and their physiological impact remain poorly understood. In this context, the Drosophila model has not yet been widely used, but it is highly relevant and the first results indicate that it can generate new concepts. The elucidation of the metabolism and fluxes of branched-chain amino acids is beginning to shed light on the mysterious connections between clock, sleep, and metabolism, opening the possibility of new therapies.