** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** NONALCOHOLIC FATTY LIVER DISEASE (NAFLD) IS THE MOST COMMON CAUSE OF LIVER DISEASE IN THE UNITED STATES, AFFECTING APPROXIMATELY 80 MILLION ADULTS. IMPORTANTLY, RISK FACTORS FOR THE DEVELOPMENT OF NAFLD TEND TO INCREASE IN PREVALENCE WITH ADVANCING AGE. THE PATHOGENESIS OF NAFLD HAS BEEN CONSIDERED AS DEVELOPING FROM PREVALENT MULTIPLE PARALLEL FACTORS, INCLUDING GUT-LIVER AXIS, INFLAMMATORY PATHWAYS, AND THE HIGH-FAT WESTERN DIETS. NAFLD DISPLAYS KEY CHARACTERISTICS, SUCH AS INTESTINAL DYSBIOSIS AND GUT PERMEABILITY. IDENTIFICATION OF PREVIOUSLY UNRECOGNIZED MOLECULES CONTRIBUTING TO NAFLD VIA GUT-LIVER AXIS WILL HELP TO UNDERSTAND THE ACTION MECHANISMS FURTHER AND TO DEVELOP EFFICIENT PREVENTION STRATEGIES. GROWING EVIDENCE INDICATES THAT THE ENDOCANNABINOID SYSTEM (ECS) IS INTIMATELY INVOLVED IN THE DEVELOPMENT OF OBESITY AND TYPE 2 DIABETES (T2D), THE EARLIEST METABOLIC DRIVER OF NAFLD, MAINLY BY ACTIVATING THE CANNABINOID 1 RECEPTOR (CB1R) TO TARGET CENTRAL AND PERIPHERAL SITES SUCH AS THE LIVER. THE PREVIOUS STUDIES DISCOVERED THAT L-THEANINE, A NON-PROTEIN WATER-SOLUBLE AMINO ACID CHARACTERISTICALLY FOUND IN TEA PLANTS, CAN BIND TO CB1R AND INHIBIT ITS ACTIVITY. THUS, THE OBJECTIVE OF THIS PROJECT IS TO DETERMINE THE ROLE OF CB1R VIA GUT-LIVER AXIS IN THE TEA BIOACTIVITIES. THE RESULTS OF THIS PROJECT WILL HAVE SIGNIFICANT IMPLICATIONS BY PROVIDING FUNDAMENTAL GUIDELINES AND JUSTIFICATION FOR DEVELOPMENT OF FUTURE PROJECTS EXAMINING THE EFFECTS OF FOOD AND GUT HEALTH ON NAFLD.