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.

L-Theanine can regulate the immune system's function and inflammatory responses under heat stress via activation of the p38 MAPK signalling pathway.

Heat stress caused by heatwaves, extreme temperatures, and other weather can damage the intestinal barrier of organisms. L-Theanine (LTA) attenuates heat stress-induced oxidative stress, inflammatory responses, and impaired immune function, but its protective effect on the intestinal barrier of heat-stressed organisms is unclear. In this study, low (100 mg kg⁻¹ d⁻¹), medium (200 mg kg⁻¹ d⁻¹), and high (400 mg kg⁻¹ d⁻¹) dosages of LTA were used in the gavage of C57BL/6J male mice that were experimented on for 50 d. These mice were subjected to heat stress for 2 h d⁻¹ at 40 ± 1 °C and 60 ± 5% RH in the last 7 d. LTA attenuated the heat stress-induced decreases in body mass and feed intake, and the destruction of intestinal villi and crypt depth; reduced the serum levels of FITC-dextran and D-LA, as well as the DAO activity; and upregulated the colonic tissues of Occludin, Claudin-1, and ZO-1 mRNA and occludin protein expression. The number of goblet cells in the colon tissue of heat-stressed organisms increased in the presence of LTA, and the expression levels of Muc2, Muc4 mRNA, and Muc2 protein were upregulated. LTA increased the abundance of Bifidobacterium and Turicibacter, and decreased the abundance of Enterorhabdus and Desulfovibrio in the intestinal tract of heat-stressed organisms and restored gut microbiota homeostasis. LTA promoted the secretion of IL-4, IL-10, and sIgA and inhibited the secretion of TNF-α and IFN-γ in the colon of heat-stressed organisms. The expressions of Hsf1, Hsp70, Hsph1, TLR4, P38 MAPK, p-P65 NF-κB, MLCK mRNA, and proteins were downregulated by LTA in the colon of heat-stressed organisms. These results suggest that LTA protects the intestinal barrier in heat-stressed organisms by modulating multiple molecular pathways. Therefore, this study provides evidence on how tea-containing LTA treatments could be used to prevent and relieve intestinal problems related to heat stress.

The intestine is a key organ for the absorption of amino acids. L-theanine (LTA) is a structural analog of glutamine and a characteristic non-protein amino acid found in tea (Camellia sinensis) that regulates lipid and protein metabolism. The present study explored the role of LTA in intestinal amino acid absorption, protein synthesis, and its mechanisms. Overall, our findings suggest that LTA supplementation not only affects serum alkaline phosphatase (AKP), total protein (TP), and urea nitrogen (BUN) levels, but it also upregulates the mRNA and protein expression of amino acid transporters (EAAT3, EAAT1, 4F2hc, y⁺LAT1, CAT1, ASCT2, and B⁰AT1), and activates the mTOR signaling pathway. The downstream S6 and S6K1 proteins are regulated, and the expression of amino acid transporters is regulated. These findings suggest that LTA increases intestinal AA absorption, promotes protein metabolism, and increases nitrogen utilization by upregulating AAT expression, activating the mTOR signaling pathway, and phosphorylating the mTOR downstream proteins S6 and S6K1.

L-Theanine alleviated heat stress-induced proteotoxicityviaHsf1/Hsp70 and heat stress-induced metabolic stress by acting on the interaction of Hsf1–AMPK.