Regulatory Effects and Mechanisms of L-Theanine on Neurotransmitters via Liver-Brain Axis Under a High Protein Diet

Abstract

Excessive protein intake causes liver and brain damage and neurotransmitter disorders, thereby inducing cognitive dysfunction. L-theanine can regulate the neurotransmitter content and show great potential in liver and brain protection. However, it remains unclear whether l-theanine effectively regulates neurotransmitter content under high-protein diet. A 40-day feeding experiment was performed in Sprague Dawley rats to investigate the regulatory effects and mechanisms of l-theanine on neurotransmitters via liver-brain axis in high-protein diets. The results showed that a 30% protein diet increased the liver and brain neurotransmitter content while maintaining the normal structure of liver and the hippocampal CA1 of brain and improving the autonomous behavior of rats. In contrast, 40% and 50% protein diets decreased the content of neurotransmitters, affected autonomous behavior, destroyed the hippocampal CA1 of brain structure, increased hepatic inflammatory infiltration, lipid degeneration, and hepatocyte eosinophilic change in liver, increased liver AST, ALT, MDA, CRP, and blood ammonia level, and decreased liver SOD and CAT level. However, l-theanine improved liver and brain neurotransmitter content, autonomous behavior, liver and hippocampal brain structure, and liver biochemical indicators in 40% and 50% protein diets. To explore how LTA can eliminate the adverse effects of a high-protein diet, we analyzed different metabolites and proteomes and using western blotting for validate quantitatively. We found that l-theanine regulates the activity of PF4 and G protein subunit alpha i2, increases the content of brain-derived neurotrophic factor and dopamine under a 20% protein diet. In addition, l-theanine can activate the adenylate cyclase-protein kinase A pathway through the protein alpha/beta-hydrolase domain protein 12 to regulate the content of neurotransmitters under a 40% protein diet, thereby exerting a neuroprotective effect.

Keywords: High protein diet; L-Theanine; Neurotransmitters; Nutritional intervention.