Gerrard, Samuel David2024-12-202024-12-202024-12-19vt_gsexam:41787https://hdl.handle.net/10919/123852Medium chain-fatty acids (MCFA) are a group of fatty acids containing hydrocarbon chains between 6-12 carbons. They are rapidly absorbed and taken up by cells which has led to their incorporation into neonatal formulas as an alternative source of energy. While abundant literature is available on proposed beneficial effects of MCFA at low levels of incorporation, little is known about utilization of MCFAs in formulas and the effects on growth and liver health. Therefore, we set out to test the hypothesis that MCFAs are metabolized differently than long-chain fatty acids (LCFAs) when they are the main energy substrate of the formula. We sought to investigate the mechanism that differentiates MCFA from LCFA from a metabolic and physiologic standpoint. Feeding high-fat diets of MCFA and LCFA resulted in steatosis from both classes of fatty acids. However, MCFA fed group accumulated 4  more fat in their livers than the LCFA group. Steatosis was accompanied by decreased - oxidation and increased expression of fatty acid synthetic enzymes in MCFA pigs. Peripherally, skeletal muscle displayed an upregulation of cholesterol-related genes. Lowering the amount of MCFA in the formula relieved hepatic steatosis however, only removing the MCFA source entirely from the diet lowered the steatosis below 20% of liver weight. Isolated mitochondria from pigs fed high MCFA formula were unable to oxidize pyruvate and malate as effectively as pigs without MCFA in their formula. Mitochondria also oxidized laurate more effectively when attached to carnitine. Regardless, pigs fed higher amounts of MCFA, or MCFA at any level, had higher levels of fat in their livers than the LCFA counterparts. Taken together, these data suggest that MCFA and LCFA are handled differently from a cellular perspective and MCFA changed the hepatic phenotype of neonatal pigs however, several unanswered questions arose from the completed studies.ETDenIn Copyright-oxidationlivermedium-chain fatty acidsmetabolismmitochondrianutritionnon-alcoholic fatty liver diseaseDissertation