Regulation of Mitochondrial Metabolism and Lipogenesis

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dc.contributor.advisorSunny, Nishanth Een_US
dc.contributor.authorSurugihalli, Chaitraen_US
dc.contributor.departmentAnimal Sciencesen_US
dc.contributor.publisherDigital Repository at the University of Marylanden_US
dc.contributor.publisherUniversity of Maryland (College Park, Md.)en_US
dc.date.accessioned2022-06-15T05:31:05Z
dc.date.available2022-06-15T05:31:05Z
dc.date.issued2021en_US
dc.description.abstractNon-alcoholic fatty liver disease is one of the most common liver disorders with a global prevalence of over 25%. Fatty liver is the most common comorbidity of insulin resistance, obesity, and type 2 diabetes mellitus. During fatty liver, nutrient overload and the associated hyperinsulinemia results in elevated circulating free fatty acids and lipid accumulation in the liver. High rates of lipid accumulation in the liver is partly attributed to high rates of lipogenesis from carbohydrates, together with dysfunctional lipid oxidation. Further, these dysfunctional metabolic networks will induce oxidative stress and inflammation. Thus, understanding the metabolic mechanisms contributing towards the etiology of fatty liver and its associated morbidities is of major interest towards developing prevention and management strategies. This dissertation utilizes a combination of in-vivo (chicken and mice) and in-vitro (isolated mitochondria) systems with stable isotope-based methodologies to study metabolic regulation.Chicken embryos utilize yolk lipids (>45%), deriving over 90% of their energy through lipid oxidation for development. However, during the last few days of incubation and immediately after hatch, there is a substantial induction of lipogenesis. Despite the hepatic lipid overload, the synergistic remodeling of hepatic metabolic networks during embryonic-to-neonatal development blunted inflammatory onset, prevented accumulation of lipotoxic intermediates, and reduced reactive oxygen species production. Elevated plasma branched-chain amino acids (BCAAs) are a characteristic of insulin resistance and are relevant in predicting T2DM. Defects in BCAA degradation networks are also evident in several tissues during insulin resistance and associated co-morbidities. Furthermore, alterations in BCAA metabolism are associated with changes in lipogenesis and mitochondrial oxidative networks. We utilize a combination of isolated mitochondrial systems and stable isotope tracers in diet-induced mouse models of fatty liver, to determine its impact on mitochondrial metabolism and lipogenesis. In summary, the dissertation highlights i) the importance of the natural but dynamic remodeling of hepatic mitochondrial metabolism and lipogenesis during the efficient embryonic-to-neonatal transition in chicken ii) the significance of BCAAs as important regulators of hepatic mitochondrial lipid metabolism. Thus, these studies provide a platform to modulate hepatic metabolic networks and utilize the embryonic-to-neonatal transition phase and dietary intervention of BCAAs as management strategies to alleviate metabolic dysfunctions. en_US
dc.identifierhttps://doi.org/10.13016/swee-jilz
dc.identifier.urihttp://hdl.handle.net/1903/28688
dc.language.isoenen_US
dc.subject.pqcontrolledNutritionen_US
dc.subject.pqcontrolledHealth sciencesen_US
dc.subject.pquncontrolledFatty liver diseaseen_US
dc.subject.pquncontrolledInsulin resistanceen_US
dc.subject.pquncontrolledLiver metabolismen_US
dc.subject.pquncontrolledMetabolic diseaseen_US
dc.subject.pquncontrolledMitochondriaen_US
dc.subject.pquncontrolledObesityen_US
dc.titleRegulation of Mitochondrial Metabolism and Lipogenesisen_US
dc.typeDissertationen_US

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