L-Leucine

L-Leucine is an essential branched-chain amino acid (BCAA), which activates the mTOR signaling pathway^[1]. IC50 & Target:mTORC1^[1] In Vitro: L-Leucine (10 mM) treatment impairs endocrine progenitor cell development^[1].
In E13.5 rat pancreatic explants, in absence of added L-Leucine, Ngn3 mRNA levels increased after 1 day of culture, peaked on day 3, and then decreased. When L-Leucine is added, a dramatic decrease is observed in Ngn3 mRNA levels. This decrease in Ngn3 mRNA levels was paralleled by a decrease in the number of Ngn3-expressing cells (4728±408 vs. 959±28; P<0.01). Finally, L-Leucine also caused a dose-dependent repressive effect on the mRNA levels of the three genes, namely Ngn3, its target Insm1, and insulin^[1].
Leucine stimulates protein synthesis in skeletal muscle of neonatal pigs by enhancing mTORC1 activation. L-Leucine increases intracellular HIF-1α levels and activates the HIF-1α signaling pathway, and these two effects are mediated by the mTOR signaling pathway. This process results in Ngn3 repression and, consequently, decreases β-cell differentiation^[1].
L-leucine stimulates mTORC1 by through a mechanism that involves the leucyl tRNA synthase promoting the activity of GTP activating proteins that act on mTORC1^[2].
In Vivo: L-Leucine (24 g/kg diet) combined with Resveratrol (12.5 mg/kg diet) to diet-induced obese (DIO) mice increases adipose Sirt1 activity^[2].
Combination results in significant reductions in body weight, weight gain, visceral adipose tissue mass, fat oxidation and heat production in mice^[2].