Leucine and glycine significantly prevented triglyceride accumulation in macrophages, by inhibiting triglyceride-rich very-low-density lipoprotein (VLDL) uptake and triglyceride biosynthesis rate, while glutamine showed the opposite effects, accompanied by a concurrent upregulation of diacylglycerol acyltransferase-1 (DGAT1). Leucine also decreased macrophage cholesterol content by inhibiting the rate of cholesterol biosynthesis and increasing serum-mediated cholesterol efflux from macrophages, whereas glutamine increased the uptake of cholesterol-rich low-density lipoproteins (LDL), with concomitant accumulation of cholesterol mass. Macrophage mitochondrial respiration and ATP production were improved after leucine supplementation. Red-colored up-arrows (indicating increase or upregulation) and compounds names, designate pro-atherogenic effects; green-colored up-arrows, crossed circles (indicating decrease or inhibition), and compounds names, designate anti-atherogenic effects. ABCA1, ABCG1, ATP-binding cassette subfamily A or G member 1; DGAT1, diacylglycerol acyltransferase-1; FA, fatty acids; HDL, high-density lipoprotein; LDL, low-density lipoprotein; LDLR, LDL receptor; SR-B1, scavenger receptor type B-1; TG, triglycerides; VLDL, very-LDL.