**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 HAS REACHED EPIDEMIC PROPORTIONS, AND IS AN EXPANDING PROBLEM WORLD-WIDE. EVEN THOUGH MOST OVERWEIGHT PEOPLE CAN LOSE SOME WEIGHT IN THE SHORT TERM BY CHANGING THEIR DIET AND EXERCISE HABITS, MAINTAINING WEIGHT LOSS THROUGH DIET AND EXERCISE ALONE IS EXTREMELY DIFFICULT, AND MOST PEOPLE WILL REGAIN SOME OF THE WEIGHT LOST. EXTREME DIETS ARE HARD TO SUSTAIN, AND WEIGHT LOSS TRAINS THE BODY TO HOLD ON TO ANY EXCESS ENERGY, WHICH THEN MAKES IT EVEN HARDER TO LOSE WEIGHT. THERE ARE SOME SUCCESSFUL INTERVENTIONS FOR OBESITY TREATMENT, INCLUDING BARIATRIC SURGERY AND PHARMACEUTICAL DRUGS, BUT THESE ARE TYPICALLY RESERVED FOR THE SEVERELY OBESE, LEAVING PEOPLE WITH MILD TO MODERATE OVERWEIGHT WITH FEW OPTIONS. THEREFORE, WE ARE IN DESPERATE NEED DEVELOPING NEW STRATEGIES FOR WEIGHT LOSS. WE ARE BEGINNING TO UNDERSTAND THAT THE TRILLIONS OF BACTERIA THAT LIVE IN OUR GUTS, CALLED THE GUT MICROBIOTA, PLAY A VERY IMPORTANT ROLE IN MAINTAINING OUR BODY WEIGHT. WE ALSO KNOW THAT THE COMPOSITION OF OUR DIET IS VERY IMPORTANT IN SHAPING OUR GUT MICROBIOTA AND MAINTAINING ITS HEALTH. IN THIS PROPOSAL, WE WILL TEST WHETHER A PARTICULAR TYPE OF FAT THAT IS KNOWN TO CAUSE WEIGHT LOSS DOES SO BY CHANGING OUR GUT MICROBIOTA. THIS TYPE OF FAT, CALLED CONJUGATED LINOLEIC ACID (CLA), IS FOUND IN DAIRY AND BEEF PRODUCTS, AND IS ALSO MARKETED AS A WEIGHT LOSS SUPPLEMENT. IN THIS PROPOSAL, WE WILL USE OBESE ANIMAL MODELS TO DETERMINE IF THIS REMARKABLE DIETARY FAT TRIGGERS WEIGHT LOSS BY CHANGING THE GUT BACTERIA. TO CONFIRM THAT THE GUT BACTERIA ARE IMPORTANT FOR WEIGHT LOSS BY CLA, WE WILL ALSO USE OBESE MICE TO DETERMINE IF CHANGING THE GUT BACTERIA THROUGH THE USE OF PROBIOTICS CAN LEAD TO WEIGHT LOSS. IT IS POSSIBLE THAT THIS PROPOSAL WILL RESULT IN THE IDENTIFICATION OF NEW PROBIOTIC THERAPIES THAT COULD PROMOTE WEIGHT LOSS, GIVING PEOPLE WITH MILD TO MODERATE OVERWEIGHT A RELATIVELY SIMPLE AND INEXPENSIVE STRATEGY TO REGAIN HEALTH.