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Hepatic Lipid metabolism in Neonatal Pigs

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dc.contributor.authorGerrard, Samuel Daviden
dc.contributor.committeechairEl-Kadi, Samer Wassimen
dc.contributor.committeememberHanigan, Mark Danielen
dc.contributor.committeememberCorl, Benjamin A.en
dc.contributor.committeememberCraige, Siobhanen
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2024-12-20T09:00:57Zen
dc.date.available2024-12-20T09:00:57Zen
dc.date.issued2024-12-19en
dc.description.abstractMedium 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.en
dc.description.abstractgeneralMedium-chain fatty acids (MCFAs) are a group of molecules that contain between 6 to 12 carbon units. These fatty acids are readily available for cells to use for energy and because of this, MCFAs are commonly added to infant formulas to increase nutrient availability for infants. Using MCFAs at low levels in experimental diets has been heavily researched however, there is not much information related to feeding high amounts of MCFAs. So, we set out to determine whether MCFAs are handled the same as long-chain fatty acids (LCFAs) at higher levels in experimental formulas. Our goal was to understand how MCFA are different from LCFA in their utilization and circulation. Feeding high amounts of MCFA and LCFA resulted in fat accumulation in the liver of neonatal pigs however, pigs that were fed MCFA had higher fat content in their livers. Livers from these pigs also had a lower ability to use fatty acids for energy and had higher mRNA expression of enzymes to make more lipids. Feeding less MCFA helped to lower the amount of fat in the liver. The ability of the mitochondria to breakdown MCFA from these pigs was lower than pigs fed more LCFA. Overall, these studies highlight that high levels of MCFA lead to fat accumulation in the liver; more work needs to be done to understand the disease process.en
dc.description.degreeDoctor of Philosophyen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:41787en
dc.identifier.urihttps://hdl.handle.net/10919/123852en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subject-oxidationen
dc.subjectliveren
dc.subjectmedium-chain fatty acidsen
dc.subjectmetabolismen
dc.subjectmitochondriaen
dc.subjectnutritionen
dc.subjectnon-alcoholic fatty liver diseaseen
dc.titleHepatic Lipid metabolism in Neonatal Pigsen
dc.typeDissertationen
thesis.degree.disciplineAnimal and Poultry Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.nameDoctor of Philosophyen

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