**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** OBESITY IS A CHRONIC PROGRESSIVE DISEASE THAT LEADS TO THE DEVELOPMENT OF TYPE 2 DIABETES, HEART DISEASE, AND STROKE, ALL OF WHICH ARE AMONG THE TOP 10 LEADING CAUSES OF DEATH IN THE U.S. CURRENTLY, LIFESTYLE MODIFICATION, INCLUDING DIET, EXERCISE, AND BEHAVIOR THERAPY, HAS REMAINED THE FIRST OPTION TO EFFECTIVELY AND SAFELY CONTROL THE PROGRESSION OF OBESITY AND OBESITY-RELATED DISEASES. HOWEVER, LOW ADHERENCE TO LIFESTYLE INTERVENTIONS UNDERSCORES THE URGENCY TO DEVELOP OTHER STRATEGIES TO COMBAT OBESITY. WE ARE THE FIRST RESEARCH GROUP TO INVESTIGATE THE NUTRACEUTICAL VALUES OF DIETARY EXOSOME-LIKE NANOPARTICLES (ELNS) IN OBESITY. WE FOUND THAT CHIVE-DERIVED ELNS (C-ELNS) IMPROVE METABOLIC HEALTH IN DIET-INDUCED OBESE MICE. CONTINUING ALONG THIS LINE OF RESEARCH, IN THIS PROJECT WE WILL INVESTIGATE (1) THE BIOAVAILABILITY AND DISTRIBUTION OF C-ELNS IN VIVO; (2) ABSORPTION OF C-ELNS IN INTESTINAL EPITHELIAL CELLS; AND (3) THE IMPACT OF C-ELNS ON THE GUT MICROBIOME IN OBESITY. SUCCESSFUL COMPLETION OF THE PROPOSED RESEARCH WILL PROVIDE MECHANISTIC INSIGHTS INTO HOW C-ELNS DISTRIBUTE AND FUNCTION IN VIVO AND PAVE THE WAY FOR APPLYING C-ELNS TO COMBAT OBESITY.