DESPITE SEVERAL ADVANCES IN NUTRITION, MANAGEMENT, GENETICS AND ANIMAL HEALTH MANAGEMENT A CONSIDERABLE NUMBER OF DAIRY COWS STILL SUFFER FROM METABOLIC INSUFFICIENCY AND METABOLIC DISEASE DURING THE TRANSITION TO LACTATION. THESE DISORDERS ARE OFTEN LINKED TO INADEQUATE LIVER FUNCTION CAUSED BY METABOLIC STRESS AND ARE MOST APPARENT AROUND THE TIME OF CALVING. THE GOAL OF THIS PROJECT IS TO DETERMINE ASPECTS OF ENERGY AND GLUCOSE METABOLISM IN LIVER OF DAIRY COWS THAT FAVOR A SUCCESSFUL TRANSITION TO LACTATION. WE HYPOTHESIZE THAT THESE PROCESSES ARE LINKED TO THE COORDINATION OF THE SYNTHESIS AND RELEASE GLUCOSE AND THE CAPACITY OF LIVER TO UTILIZE FATTY ACIDS FOR ENERGY METABOLISM. FURTHERMORE WE HYPOTHESIZE THAT METABOLIC CAPACITY IN DAIRY COWS IS DETERMINED BY THE RELATIVE ACTIVITIES OF TWO KEY ENZYMES LINKED TO THE TCA CYCLE, PYRUVATE CARBOXYLASE (PC) PHOSPHOENOLPYRUVATE CARBOXYKINASE (PCK).WE WILL EXPLORE THE EFFECTS OF MODULATING THE RELATIVE ABUNDANCE OF THESE KEY ENZYMES SPECIFICALLY AT THE LEVEL OF EXPRESSION OF THEIR GENES AND WILL DETERMINE THE EFFECT OF DELIBERATE CHANGES IN THE RATIO OF PC TO PCK ON THE ABILITY OF LIVER TO SYNTHESIZE GLUCOSE AND REGULATE ENERGY METABOLISM. WE EXPECT TO UNCOVER THE BASIC BIOLOGY FOR CONTROL OF THESE KEY GENES (PC AND PCK1) IN LIVER METABOLISM AND IDENTIFY PROPERTIES OF FATTY ACIDS AND PROPIONATE THAT REGULATE THEIR FUNCTION. THIS WORK WILL BE USED TO INFORM FUTURE DIET AND MANAGEMENT INTERVENTION STRATEGIES AND TO DEVELOP DIAGNOSTICS FOR TRANSITION COWS THAT REDUCE POOR HEALTH AND PRODUCTION OUTCOMES DURING THE TRANSITION TO LACTATION. THE KNOWLEDGE GAINED FROM THIS WORK WILL LEAD TO A GREATER UNDERSTANDING THE MOLECULAR PHYSIOLOGY OF LIVER METABOLISM AND PROCESSES THAT PRECIPITATE METABOLIC DISORDERS AND IMPAIRED PRODUCTIVITY THAT IS VITAL TO DEVELOPING STRATEGIES TO BETTER MANAGE THE HEALTH AND ECONOMIC EFFICIENCY OF DAIRY PRODUCTION.