![]() ![]() ![]() Recent studies have shown that the enzyme that catalyzes the ligation of leucine to its transfer RNA (tRNA) is responsible for sensing leucine cellular levels and activating the Rag complex. This interaction changes the intracellular localization of mTOR to a compartment that also contains the Ras homolog enriched in brain (Rheb) protein, which leads to mTORC1 complex activation. The presence of amino acids activates Rag GTPase heterodimers, which interact with Raptor. However, amino acid-dependent mTORC1 activation occurs through the Rag complex ( Figure 1). ![]() Hormones such as insulin and insulin growth factor-1 (IGF-1) activate the mTORC1 complex primarily through the TSC complex. mTORC1 has two major mechanisms of activation, via the tuberous sclerosis complex (TSC1/2) and the Rag complex. This protein complex is an important nutrient sensor that is regulated by amino acids (especially by leucine) as well as by growth factors and hormones that are secreted in response to nutrient ingestion ( i.e., insulin). mTOR controls protein synthesis through mTOR complex 1 (mTORC1), which comprises mTOR itself and other proteins, as follows: regulatory-associated protein of mTOR (Raptor), mammalian lethal with SEC13 protein 8 (MLST8), proline-rich Akt/PKB substrate 40 kDa (PRAS40), and DEP domain-containing mTOR-interacting protein (DEPTOR) ( Figure 1). mTOR is a serine/threonine kinase that is involved in the regulation of multiple cellular processes, including protein synthesis and cell growth, proliferation, and survival. Classical studies have shown that the regulation of mRNA translation by leucine is dependent on the mammalian target of rapamycin (mTOR) because rapamycin, a specific mTOR inhibitor, is able to blunt the effects of leucine. The initiation of mRNA translation is the major mechanism by which leucine stimulates protein synthesis. Although protein synthesis can be stimulated by several isolated amino acids, leucine has a particularly potent effect. Intracellular Mechanisms Activated by Leucineįor decades, amino acids have been known to be important regulators of protein synthesis. Thus, the objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of leucine supplementation in the regulation of food intake, energy balance, and glucose homeostasis.Ģ. Because leucine availability influences signaling pathways involved in the regulation of metabolism and because the incidence of metabolic diseases has reached alarming levels worldwide, investigating nutritional supplements that are potentially beneficial for the treatment and prevention of obesity and diabetes mellitus has become of paramount importance. Therefore, leucine supplementation has been studied in a variety of conditions such as aging, muscle lesions, protein/energy deprivation, obesity, and diabetes mellitus. However, leucine can also regulate several cellular processes such as protein synthesis, tissue regeneration, and metabolism. Additionally, similarly to other amino acids, the carbon skeleton of leucine can be used to generate ATP. Leucine is an essential amino acid for protein synthesis. This is the case for the branched-chain amino acid (BCAA) l-leucine (in this manuscript, we will use the term leucine). Several nutrients have nutritional properties that exceed their roles as energy sources or molecule precursors. Finally, although several studies have found that leucine supplementation improves glucose homeostasis, the underlying mechanisms involved in these potential beneficial effects remain unknown and may be partially dependent on weight loss. However, more studies are necessary to assess the effects of leucine supplementation in already-obese subjects. Consequently, no robust evidence indicates that oral leucine supplementation significantly affects food intake, although several studies have shown that leucine supplementation may help to decrease body adiposity in specific conditions. Based on the available evidence, we conclude that although central leucine injection decreases food intake, this effect is not well reproduced when leucine is provided as a dietary supplement. ![]() The objective of the present review was to summarize and discuss the available evidence regarding the mechanisms and the effects of leucine supplementation on the regulation of food intake, energy balance, and glucose homeostasis. Because mTOR signaling regulates several aspects of metabolism, the potential of leucine as a dietary supplement for treating obesity and diabetes mellitus has been investigated. Leucine is a well-known activator of the mammalian target of rapamycin (mTOR). ![]()
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