Leucine, an essential branched amino acid, has anti-obesity effects on glucose tolerance, lipid metabolism, and insulin sensitivity. The catabolism of Leucine is a conserved regulator of physiological aging, participating in diverse physiological and pathological processes. This topic review offers an up-to-date report on the decomposition and metabolites of leucine in mammals, as α-ketoisocaproate (KIC) and β-hydroxy-β-methylbutyrate (HMB).