**AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** KETOSIS IS A WELL-KNOWN METABOLIC DISORDER OFDAIRY COWS CHARACTERIZED BY THE INABILITY OF COWS TO COPE WITH THE EXCESSIVE NEGATIVE ENERGY BALANCEHAPPENING SOON AFTER PARTURITION. CLINICALLY KETOTIC COWS HAVESIGNIFICANT MILK PRODUCTION LOSSES ANDAN INCREASED RISK TO SUFFER FROM OTHER DETRIMENTAL HEALTH CONDITIONS. IT IS ESTIMATED THAT 5 TO 15% OF DAIRY COWS IN THE U.S. SUFFERFROM THE CONDITION, TOTALINGU$110-330MILLION IN ANNUAL LOSSES TO THE DAIRY INDUSTRY.THE INVOLVEMENT OF A DYSREGULATED SKELETAL MUSCLE METABOLISMIN THE ETIOLOGY OFKETOSIS IN DAIRY COWS REMAINS UNKNOWN.THIS PROJECT WILLDELINEATE MECHANISMS BY WHICH SKELETAL MUSCLEMAY HELP MODULATE WHOLE-BODY ENERGY METABOLISM AND HOMEOSTASIS. IDENTIFYING THE INVOLVEMENT OF SKELETAL MUSCLEIN THE ETIOLOGY OF KETOSIS WILL BE FUNDAMENTAL FOR THE DEVELOPMENT OF INNOVATIVE NUTRITIONAL AND THERAPEUTIC INTERVENTIONS TO PREVENT METABOLIC DISORDERS IN DAIRY COWSWHILE IMPROVING ANIMAL PRODUCTION AND WELFARE.THE GOALS ARE TO IDENTIFY THE EFFECTSOF KETOSIS ON SKELETAL MUSCLETRANSCRIPTOME AND TO CHARACTERIZE CHANGES IN TISSUE OXIDATIVE STRESS, TRIGLYCERIDE CONTENT, INTRAMYOCELLULAR FAT ABUNDANCE, AND FATTY ACID OXIDATIVE CAPACITY. IN ADDITION, WE WILL CHARACTERIZE HOW 2 MAJOR LIPOKINESTHAT ARE ASSOCIATED WITH HEALTH IN POSTPARTUM COWSIMPACT THE TRANSCRIPTIONAL PROFILEAND FATTY ACID METABOLISM OF DIFFERENTIATED BOVINE MYOTUBES IN VITRO. WE EXPECT TO DEMONSTRATE THE ROLE OF SKELETAL MUSCLE FATTY ACID METABOLISM IN THE OVERALL METABOLIC FITNESS OF POSTPARTUM DAIRY COWS AND IN THE ETIOLOGY OF KETOSIS. RESULTS OF THIS STUDY WILL ADDRESS A SIGNIFICANTKNOWLEDGE GAP IN DAIRY SCIENCESAND ALLOW FURTHERINVESTIGATIONS OFNOVELSTRATEGIESIN THE MODULATION OF EXCESSIVE NEGATIVE ENERGY BALANCEOF POSTPARTUM COWS.