** AWARDS ISSUED PRIOR TO JANUARY 20, 2025, WERE FUNDED UNDER PREVIOUS ADMINISTRATIONS AND MAY NOT REFLECT THE PRIORITIES AND POLICIES OF THE CURRENT ADMINISTRATION.** THIS PROJECT ALIGNS WITH AFRI PRIORITIES RELATED TO ANIMAL NUTRITION, GROWTH AND LACTATION AS IT AIMS TO ENHANCE NUTRIENT UTILIZATION EFFICIENCY. HIGH NEONATAL PIGLET MORTALITY HAS REMAINED A MAJOR ECONOMIC AND ANIMAL WELFARE PROBLEM IN SWINE INDUSTRY WORLDWIDE FOR DECADES AND COLLECTIVELY COSTS THE US SWINE INDUSTRY IN EXCESS OF $2 BILLION ANNUALLY. THE PROPOSED WORK AIMS TO IMPROVE ENERGY UTILIZATION OF PIGLETS BEFORE AND AFTER BIRTH. OUR PREVIOUS RESEARCH CLEARLY SHOWED THAT THE VITAMIN-LIKE SUBSTANCE, CARNITINE, IS AN ESSENTIAL NUTRIENT FOR NEWBORN PIGS TO OPTIMIZE THEIR USE OF MILK FAT FOR ENERGY. BECAUSE MATERNAL CARNITINE IS THE ONLY CARNITINE SOURCE FOR NEWBORN PIGS, WE WILL EVALUATE MATERNAL CARNITINE TRANSFER ACROSS THE PLACENTA AND MAMMARY GLAND. WE WILL EXAMINE THE EFFECTS OF INCREASING GENE EXPRESSION OF THE ORGANIC CATION TRANSPORTERS SPECIFIC FOR CARNITINE (OCTNS) ON CARNITINE TRANSPORT AND THE USE OF FAT FOR ENERGY. RESEARCH WILL FURTHER EXPLORE THE REGULATORY ROLE OF OCTNS IN CARNITINE TRANSPORT WITHIN PLACENTA, MAMMARY TISSUE AND INTESTINE USING THE ISOLATED TISSUES IN CULTURE. OUR SPECIFIC AIMS ARE: 1) TO EVALUATE THE EFFECT OF INCREASING OCTNS EXPRESSION ON MATERNAL CARNITINE STATUS, PLACENTAL CARNITINE TRANSFER, AND FAT OXIDATION, 2) TO EVALUATE THE EFFECT OF INCREASING OCTNS EXPRESSION ON PIGLET INTESTINAL CARNITINE UPTAKE, CARNITINE STATUS AND FAT OXIDATION, 3) TO INVESTIGATE THE ROLE OF OCTNS IN INCREASING MATERNAL CARNITINE TRANSFER IN MATERIAL PLACENTA, AND MAMMARY GLAND AND IN PIGLET INTESTINE AND 4) TO DETERMINE THE DIETARY CARNITINE REQUIREMENT OF SOWS BY EVALUATING CARNITINE CONTENT IN COMMERCIAL SOW DIETS, AND TO EVALUATING THE EFFECT OF INCREASING DIETARY CARNITINE LEVEL AND OCTNS EXPRESSION ON ENERGY UTILIZATION OF FETAL AND SUCKLING PIGS. IN THE AIMS OF 1-2 WE WILL EXPECT TO INCREASE MATERNAL CARNITINE TRANSFER, OFFSPRING UPTAKE AND FAT OXIDATION BY INCREASING OCTNS EXPRESSION. WE WILL EXPECT THE ROLE OF OCTNS IN CARNITINE TRANSFERWILL BE DEFINED IN THE AIM 3 BY MODIFYING OCTNS EXPRESSION USING INDUCERS AND INHIBITORS. IN THE FINAL AIM WE EXTEND PREVIOUS OUTCOMES TO PRACTICAL COMMERCIAL APPLICATION. COLLECTIVELY THIS RESEARCH WILL LEAD TO IMPROVED ENERGY USE BY THE NEONATAL PIG, RESULTING IN IMPROVED SURVIVABILITY.