The Association Between Hepatic Steatosis and Glucose Metabolic Dysfunction

dc.contributor.authorShafron, Anthony J.en
dc.contributor.committeechairEl-Kadi, Samer Wassimen
dc.contributor.committeememberJohnson, Sally E.en
dc.contributor.committeememberRhoads, Robert P.en
dc.contributor.departmentAnimal and Poultry Sciencesen
dc.date.accessioned2025-06-07T08:04:33Zen
dc.date.available2025-06-07T08:04:33Zen
dc.date.issued2025-05-22en
dc.description.abstractNon-alcoholic fatty liver disease (NAFLD) is a growing global concern especially in Western countries, primarily resulting from poor nutritional habits. This disorder can manifest as early as the neonatal period suggesting that even in that period nutrition may play a role. While previous reports demonstrated that formulas rich in medium-chain fatty acids (MCFAs) play a significant role in the NAFLD development in a neonatal pig model by comparison to long-chain fatty acid (LCFA). However, how the energy content of these formulas influences NAFLD pathogenesis remains unclear. Our hypothesis was that MCFAs induce NAFLD in neonatal pigs independent of energy content, and that MCFA-induced NAFLD disrupts hepatic glucose metabolism through dysregulation of key glucose metabolic and insulin signaling pathways. Pigs (n = 6) were fed either MCFA or LCFA at high or low inclusion levels for 20 d in a 2 × 2 factorial design. Fractional body weight increased throughout the experimental period and was greater for pigs fed the LCFA compared with those fed the MCFA formulas on day 21 (P < 0.01). Although pigs fed LCFA formulas maintained similar body weights regardless of energy content, those on high-energy formulas had less lean and greater fat mass (P < 0.05). The same pattern occurred in MCFA-fed pigs, where similar body weights masked a shift from lean to fat mass in the high-energy group (P < 0.05). Hepatic fat percentage was greater in MCFA-fed than LCFA-fed pigs (P < 0.0001) and greater in high-energy versus low-energy groups (P < 0.0001). The key lipogenic transcription factors involved in regulating lipogenic and lipolytic pathways were upregulated in response to greater energy content regardless of fat type, along with their downstream target genes (P < 0.05). However, DNL index was greater for pigs fed the MCFA compared with those fed LCFA (P < 0.0001). The relative mRNA expression of glycolytic, and gluconeogenic genes was upregulated in high energy fed pigs (P < 0.05), without any significant differences in blood glucose and insulin concentrations. Our data suggest that while excess energy contributes to hepatic steatosis, MCFAs are a primary driver of this condition independent of caloric content, with consequential effects on hepatic glucose metabolism.en
dc.description.abstractgeneralFatty liver disease occurs when too much fat accumulates in the liver and is prevalent in North America because of unhealthy diets. Studies indicated that this problem could begin as early as infancy, potentially influenced by the types of fat in baby formulas. In our study, we used piglets to represent human infants and tested how different formula compositions affect liver health. We compared formulas containing either coconut oil (which has medium-chain fatty acids) or lard (which has long-chain fatty acids) at both high- and low-calorie levels. Our key finding was that piglets fed coconut oil-based formulas developed fatty liver disease regardless of calories in the formula, though high-calorie formulas worsened the condition. The coconut oil-based formulas changed how the liver breaks down fats and sugars and disrupted their normal metabolism, even while blood glucose levels remained normal. These findings highlight the importance of considering fat composition in infant formulas to prevent liver problems that may begin in early life, suggesting that the type of fat matters more than we previously understood for long-term health of the liver.en
dc.description.degreeMaster of Scienceen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:44032en
dc.identifier.urihttps://hdl.handle.net/10919/135411en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectmedium-chain fatty acidsen
dc.subjectlong-chain fatty acidsen
dc.subjectpigen
dc.titleThe Association Between Hepatic Steatosis and Glucose Metabolic Dysfunctionen
dc.typeThesisen
thesis.degree.disciplineAnimal and Poultry Sciencesen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.levelmastersen
thesis.degree.nameMaster of Scienceen

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