DURING THE PERIPARTURIENT PERIOD OF DAIRY COWS, ADIPOSE TISSUES (AT) BREAKDOWN OF FAT RESERVES (STORED AS TRIGLYCERIDES) FULFILLS, IN PART, ENERGY DEFICITS DRIVEN BY CALF GROWTH AND MILK PRODUCTION.THE BREAKDOWN OF TRIGLYCERIDES INTO FREE FATTY ACIDS AND GLYCEROL IS TERMED LIPOLYSIS. WHEN LIPOLYSIS OCCURS, IT INDUCES CHANGES IN THE STRUCTURE OF AT THAT ARE CHARACTERIZED BY A MODERATE INFLAMMATORY RESPONSE WITH INFILTRATION OF IMMUNE CELLS SPECIALLY MACROPHAGES.EXTENDED PERIODS OF LIPOLYSIS LEAD TO EXCESSIVE INFLAMMATION IN AT AND AS A CONSEQUENCE COWS HAVE POOR LACTATION PERFORMANCE AND ARE PREDISPOSED TO DISEASE. EXCESSIVE INFLAMMATION IN AT CAUSES IMPORTANT ECONOMIC LOSSES TO DAIRY PRODUCERS AND IMPACTS NEGATIVELY THE WELLBEING AND HEALTH OF DAIRY COWS.DURING LIPOLYSIS FAT CELLS, ALSO KNOWN AS ADIPOCYTES, SECRETE A TYPE OF MOLECULES TERMED HYDROXYL-OCTADECADIENOIC ACIDS (HODES) THAT ARE DERIVED FROM LINOLEIC ACID. THESE HODES ARE POTENT MODULATORS OF INFLAMMATION IN AT AND MAY DIRECTLY INCREASE LIPOLYSIS RATE BY REDUCING ADIPOCYTE RESPONSE TO INSULIN (THE ANTI-LIPOLYSIS HORMONE). OUR HYPOTHESIS IS THAT LIPOLYSIS DYSREGULATION INCREASES THE ABUNDANCE OF HODES IN AT WHICH ENHANCES AT MACROPHAGE INFILTRATION AND SUSTAINS AT INFLAMMATION. WE WILL DEVELOP THE HYPOTHESIS IN TWO AIMS. AIM 1 WILL DETERMINE HOW HODES SYNTHESIZED DURING LIPOLYSIS IN COWS' AT MODIFY MACROPHAGE INFLAMMATORY RESPONSE AND REDUCE THE FAT CELLS SENSITIVITY TO INSULIN. AIM 2 WILL DETERMINE THE EFFECT OF LIPOLYSIS INHIBITION USING NIACIN (A NUTRITIONAL SUPPLEMENT) IN PERIPARTURIENT DAIRY COWS ON HODES AND AT MACROPHAGE INFLAMMATORY RESPONSES.UPON COMPLETION OF THIS PROJECT, WE WILL BE ABLE TO DETERMINE THE ROLE OF HODES IN THE VICIOUS CYCLE OF LIPOLYSIS DYSREGULATION AND CHRONIC INFLAMMATION IN AT. THESE FINDINGS WILL SUPPORT THE USE OF HODES AS DIAGNOSTIC TOOL TO DETECT AT INFLAMMATION. ALSO, RESULTS FROM THIS PROJECT WILL PROVIDE SCIENTIFIC BASES FOR THE USE OF NUTRITIONAL OR PHARMACOLOGICAL COMPOUNDS THAT INHIBIT LIPOLYSIS AND WILL HELP PRODUCERS CONTROL AT INFLAMMATION IN THEIR COWS.