{"id":{"repo_id":"vt","oai_identifier":"oai:vtechworks.lib.vt.edu:10919/134998"},"canonical_url":"https://search.dev.ndltd.org/etd/vt/oai:vtechworks.lib.vt.edu:10919/134998","repository":{"repo_id":"vt","name":"Virginia Tech","base_url":"https://vtechworks.lib.vt.edu/oai/request"},"display":{"title":"The impact of NOX4 deficiency on sexually dimorphic lipid handling in HFD-challenged mice","abstract":"Dietary excess promotes metabolic dysfunction through nutrient overload. If sustained, it can impair physiological metabolic processes necessary for the proper handling of nutrients. Proper handling of nutrients depends on the capacity of an organism to properly sense, regulate, respond, and adapt to energetic demands and its energetic needs. Reactive oxygen species (ROS) are essential metabolic mediators, increasing in response to high nutrient availability and enhancing the function of proteins that regulate nutrient metabolism. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is a dynamic, pleiotropic enzyme that generates ROS in response to nutrient levels. Here we demonstrate, particularly in the liver, skeletal muscle, and bone marrow, that in conditions of nutrient overload, male mice lacking NOX4 display numerous improvements in metabolic health while females show the opposite. This work increases our understanding of factors contributing to disparities in metabolic outcomes between males and females, and underscores a role of NOX4-ROS in nutrient handling. Identifying the underlying mechanisms will aid in designing interventions to address sex-specific vulnerability and enhance resilience to nutrient overload in conditions of chronic metabolic diseases.","abstract_html":"Dietary excess promotes metabolic dysfunction through nutrient overload. If sustained, it can impair physiological metabolic processes necessary for the proper handling of nutrients. Proper handling of nutrients depends on the capacity of an organism to properly sense, regulate, respond, and adapt to energetic demands and its energetic needs. Reactive oxygen species (ROS) are essential metabolic mediators, increasing in response to high nutrient availability and enhancing the function of proteins that regulate nutrient metabolism. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is a dynamic, pleiotropic enzyme that generates ROS in response to nutrient levels. Here we demonstrate, particularly in the liver, skeletal muscle, and bone marrow, that in conditions of nutrient overload, male mice lacking NOX4 display numerous improvements in metabolic health while females show the opposite. This work increases our understanding of factors contributing to disparities in metabolic outcomes between males and females, and underscores a role of NOX4-ROS in nutrient handling. Identifying the underlying mechanisms will aid in designing interventions to address sex-specific vulnerability and enhance resilience to nutrient overload in conditions of chronic metabolic diseases.","abstract_has_math":false,"creators":["Bond, Jacob Matthew"],"institution":"Virginia Tech","degree_name":"Doctor of Philosophy","degree_level":"doctoral","degree_discipline":"Translational Biology, Medicine and Health","degree_department":"Graduate School","school":null,"contributors":[],"advisors":[],"committee_chairs":["Craige, Siobhan"],"committee_members":["Tencerova, M. Sc. Michaela","Davy, Kevin P.","Gilbert, Elizabeth Ruth"],"year":2025,"date_issued":"2025-06-02","date_published":"2025-06-02","updated_at":"2026-07-22T22:19:13Z","subjects":["Reactive oxygen species","sexual dimorphism","metabolism","liver","skeletal muscle"],"languages":["en"],"rights":["In Copyright"],"rights_urls":["http://rightsstatements.org/vocab/InC/1.0/"],"identifier_entries":[{"key":"dc:identifier.other","label":"Dc Identifier Other","values":["vt_gsexam:43749"],"render_values":[{"text":"vt_gsexam:43749","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/10919/134998","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.committeechair","label":"Committee Chair","values":["Craige, Siobhan"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Tencerova, M. Sc. 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If sustained, it can impair physiological metabolic processes necessary for the proper handling of nutrients. Proper handling of nutrients depends on the capacity of an organism to properly sense, regulate, respond, and adapt to energetic demands and its energetic needs. Reactive oxygen species (ROS) are essential metabolic mediators, increasing in response to high nutrient availability and enhancing the function of proteins that regulate nutrient metabolism. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) is a dynamic, pleiotropic enzyme that generates ROS in response to nutrient levels. Here we demonstrate, particularly in the liver, skeletal muscle, and bone marrow, that in conditions of nutrient overload, male mice lacking NOX4 display numerous improvements in metabolic health while females show the opposite. This work increases our understanding of factors contributing to disparities in metabolic outcomes between males and females, and underscores a role of NOX4-ROS in nutrient handling. Identifying the underlying mechanisms will aid in designing interventions to address sex-specific vulnerability and enhance resilience to nutrient overload in conditions of chronic metabolic diseases."]},{"key":"dc:description.abstractgeneral","label":"General Abstract","values":["Chronic overconsumption of food can overwhelm the body's ability to process nutrients properly, leading to metabolic problems like obesity and diabetes. The body relies on specialized molecules to sense and manage nutrient levels, ensuring energy is used and stored efficiently. One key player in this process is a group of molecules called reactive oxygen species (ROS), which help regulate metabolism by responding to excess nutrients and modifying proteins to maintain balance. This body of work focuses on an enzyme called NADPH oxidase 4, or, \"NOX4\", which is an enzyme that produces ROS in response to changing nutrient levels. Using mice given a diet high in fat, we found that when NOX4 was missing, male mice showed improved metabolic health, while female mice experienced the opposite effect. These findings highlight biological differences in how males and females handle excess nutrients and suggest that NOX4 plays a crucial role in these differences. Understanding the molecular basis for these observations can help develop better treatments for metabolic diseases by addressing sex-specific vulnerabilities and enhancing resilience against metabolic dysregulation."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Doctor of Philosophy"]},{"key":"dc:format.medium","label":"Dc Format Medium","values":["ETD"]},{"key":"dc:title","label":"Title","values":["The impact of NOX4 deficiency on sexually dimorphic lipid handling in HFD-challenged mice"]}]}],"canonical_facts":{"dc:contributor.committeechair":["Craige, Siobhan"],"dc:contributor.committeemember":["Tencerova, M. Sc. 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Here we demonstrate, particularly in the liver, skeletal muscle, and bone marrow, that in conditions of nutrient overload, male mice lacking NOX4 display numerous improvements in metabolic health while females show the opposite. This work increases our understanding of factors contributing to disparities in metabolic outcomes between males and females, and underscores a role of NOX4-ROS in nutrient handling. Identifying the underlying mechanisms will aid in designing interventions to address sex-specific vulnerability and enhance resilience to nutrient overload in conditions of chronic metabolic diseases."],"dc:description.abstractgeneral":["Chronic overconsumption of food can overwhelm the body's ability to process nutrients properly, leading to metabolic problems like obesity and diabetes. The body relies on specialized molecules to sense and manage nutrient levels, ensuring energy is used and stored efficiently. One key player in this process is a group of molecules called reactive oxygen species (ROS), which help regulate metabolism by responding to excess nutrients and modifying proteins to maintain balance. This body of work focuses on an enzyme called NADPH oxidase 4, or, \"NOX4\", which is an enzyme that produces ROS in response to changing nutrient levels. Using mice given a diet high in fat, we found that when NOX4 was missing, male mice showed improved metabolic health, while female mice experienced the opposite effect. These findings highlight biological differences in how males and females handle excess nutrients and suggest that NOX4 plays a crucial role in these differences. Understanding the molecular basis for these observations can help develop better treatments for metabolic diseases by addressing sex-specific vulnerabilities and enhancing resilience against metabolic dysregulation."],"dc:description.degree":["Doctor of Philosophy"],"dc:format.medium":["ETD"],"dc:identifier.other":["vt_gsexam:43749"],"dc:identifier.uri":["https://hdl.handle.net/10919/134998"],"dc:language.iso":["en"],"dc:publisher":["Virginia Tech"],"dc:rights":["In Copyright"],"dc:rights.uri":["http://rightsstatements.org/vocab/InC/1.0/"],"dc:subject":["Reactive oxygen species","sexual dimorphism","metabolism","liver","skeletal muscle"],"dc:title":["The impact of NOX4 deficiency on sexually dimorphic lipid handling in HFD-challenged mice"],"dc:type":["Dissertation"],"thesis:degree_discipline":["Translational Biology, Medicine and Health"],"thesis:degree_level":["doctoral"],"thesis:degree_name":["Doctor of Philosophy"],"thesis:institution_name":["Virginia Polytechnic Institute and State University"]},"updated_at":"2026-07-22T22:19:13Z"}