**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** INFLAMMATION UNDERLIES MANY CHRONIC DISEASES, BUT ATTEMPTS TO SUCCESSFULLY TARGET IT WITH FOOD-BASED FORMULATIONS HAVE BEEN LARGELY UNSUCCESSFUL DUE TO COMPLIANCE ISSUES AND LIMITED BIOAVAILABILITY OF FOOD-BASED SUPPLEMENTS. IS IT WELL-ESTABLISHED THAT DIETS HIGH IN THE OMEGA-3 FATTY ACID, DOCOSAHEXAENOIC ACID (DHA, 22:6N-3), ARE PROTECTIVE AGAINST INFLAMMATION. THIS IS BECAUSE IN VIVO, DHA IS CONVERTED VIA MONOOXYGENASE ENZYMES INTO BIOACTIVE, ANTI-INFLAMMATORY LIPID MEDIATORS THAT RESOLVE INFLAMMATION. HOWEVER, THE DOSE-RESPONSE RELATIONSHIP BETWEEN DHA AND INFLAMMATION IS NON-LINEAR, MEANING THAT AT A CERTAIN POINT, NO MATTER HOW MUCH DHA IS IN THE DIET, EFFICACY IS NOT INCREASED. THIS IS BECAUSE THE ENDOGENOUS TURNOVER OF DHA INTO ANTI-INFLAMMATORY LIPID MEDIATORS IS VERY SLOW IN BOTH RODENTS AND HUMANS. ONE WAY TO INCREASE AND MAINTAIN DHA-DERIVED LIPID MEDIATOR LEVELS IS BY PROVIDING THEM DIRECTLY THROUGH THE DIET. HOWEVER, THEIR BIOAVAILABILITY IS LOW BECAUSE THEY ALSO DEGRADE IN THE STOMACH. IN AN ATTEMPT TO REVOLUTIONIZE THE WAY INFLAMMATION IS TARGETED THROUGH FOOD, THIS PROPOSAL AIMS TO USE MILK FAT GLOBULES (MFGS) AS AN IN SITU GENERATOR AND STABALIZER OF ANTI-INFLAMMATORY AND PRO-RESOLVING BIOACTIVE LIPID MEDIATORS DERIVED FROM DHA, AND TEST THAT ORALLY DELIVERING THESE STABILIZED BIOACTIVE LIPIDS INCREASES BIOAVAILABILITY AND RESILIENCE TO INFLAMMATION IN AN ANIMAL MODEL OF THE METABOLIC SYNDROME. THE PROPOSED INNOVATIVE APPROACH OF GENERATING BIOACTIVE, STABLE AND BIOAVAILABLE DHA-DERIVED ANTI-INFLAMMATORY LIPID MEDIATORS VIA MFGS COULD READILY BE IMPLEMENTED INTO DAIRY FOOD SYSTEMS. BY OPTIMIZING THE ENCAPSULATION PROCESS AND ESTABLISHING THE EVIDENCE IN ANIMAL MODELS, THE PROPOSED PROJECT SERVES AS A FIRST-STEP TOWARDS ACHIEVING THIS LONG-TERM VISION OF CLINICALLY TARGETING INFLAMMATION UNDERLYING MANY CHRONIC ILLNESSES.