l-Theanine regulates glucose, lipid, and protein metabolism via insulin and AMP-activated protein kinase signaling pathways.

l-Theanine is an important component found in tea and has positive effects on nutrient absorption and transport. However, whether l-theanine can regulate glucose, lipid, and protein metabolism remains unknown. This study aims to investigate the effects of l-theanine on glucose, lipid, and protein metabolism in male Sprague-Dawley rats and characterize the underlying mechanisms. Compared to the control group, l-theanine increased the contents of hepatic and muscle glycogen, serum total protein (TP), and albumin (Alb), lowered the serum low-density lipoprotein cholesterol (LDL-C) level, decreased the activity of acetyl-CoA carboxylase (ACC), and enhanced carnitine palmitoyl transferase-1 (CPT-1) activity in the liver. Additionally, l-theanine upregulated the mRNA expression of phosphofructokinase (PFKL), CPT-1, insulin receptor (INSR), insulin receptor substrate (IRS), and liver kinase B1 (LKB1) and downregulated the mRNA expression of phosphoenolpyruvate carboxykinase 1 (PCK1), glucose-6-phosphatase catalytic subunit (G6PC), fatty acid synthase (FAS), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR). Moreover, l-theanine upregulated the expression of PFKL, glycogen synthase 2 (GYS2), ribosomal protein S6 (S6), INSR, IRS, and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) proteins; downregulated the expression of FAS, sterol regulatory element binding protein-1c (SREBP-1c), and HMGCR proteins; enhanced the phosphorylation of the mammal target of rapamycin (mTOR), ribosomal protein S6 kinase (p70S6K), protein kinase B (AKT), and AMP-activated protein kinase (AMPK); and decreased the phosphorylation of glycogen synthase kinase 3β (GSK-3β) and ACC1. Furthermore, 100 mg kg-1 l-theanine was more effective at eliciting these effects than 200 and 400 mg kg-1 l-theanine. In conclusion, l-theanine can regulate glucose, lipid, and protein metabolism via insulin and AMPK and their downstream signaling pathways.