L‐Theanine Alleviates High‐Fat Diet‐Induced Obesity by Enhancing Hepatic Oxidative Phosphorylation and Remodeling Gut Microbiota to Augment Butyrate‐Producing

Obesity represents a significant global health challenge, necessitating innovative therapeutic approaches. L-theanine, a bioactive component in tea, possesses diverse biological activities. This study investigates the anti-obesity mechanisms of L-theanine, focusing on its effects on lipid metabolism, energy expenditure, and gut microbiota using both in vitro and in vivo models. In vitro, L-theanine (2 mM) reduced hepatocyte lipid content by downregulating lipogenic genes. In vivo, 12-week supplementation with L-theanine (30 and 100 mg/kg/day) dose-dependently decreased HFD-induced body weight gain, adipose tissue mass, and serum triglycerides (TG) without altering food intake. Mechanistically, L-theanine disturbed the transcription of some key genes closely related to thermogenesis, lipid oxidation, and glycolipid metabolism, with hepatic transcriptomics confirming the enrichment of oxidative phosphorylation and thermogenic pathways. Critically, L-theanine also regulates gut microbiota, specifically increasing the abundance of Blautia and enhancing short-chain fatty acid biosynthesis. Collectively, these findings indicate that L-theanine shows promise as a multi-target therapeutic agent for obesity, regulating lipid metabolism, enhancing energy expenditure, and maintaining gut microbiota homeostasis. However, its molecular targets, mechanisms, and human applicability still remain unclear.