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Virginia Tech

The impact of NOX4 deficiency on sexually dimorphic lipid handling in HFD-challenged mice

Abstract

dc:description.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.

Degree

thesis:*
Name thesis:degree_name
Doctor of Philosophy
Level thesis:degree_level
doctoral
Discipline thesis:degree_discipline
Translational Biology, Medicine and Health
Department dc:contributor.department
Graduate School
Grantor dc:publisher
Virginia Tech
Year dc:date.issued
2025

Author and committee

dc:creator, dc:contributor.*
Author dc:creator
  • Bond, Jacob Matthew
Chair dc:contributor.committeechair
  • Craige, Siobhan
Committee members dc:contributor.committeemember
  • Tencerova, M. Sc. Michaela
  • Davy, Kevin P.
  • Gilbert, Elizabeth Ruth

Subjects

dc:subject × 5

Rights

dc:rights
Statement dc:rights
  • In Copyright
Language dc:language.iso
en

Identifiers

dc:identifier.*
Dc Identifier Other
vt_gsexam:43749
OAI identifier oai:identifier
oai:vtechworks.lib.vt.edu:10919/134998

Chain of custody

source
Harvested from
Virginia Tech
Base URL
vtechworks.lib.vt.edu/oai/request
Last updated
2026-07-22
Source record
OAI-PMH GetRecord
citation

Bond, Jacob Matthew. The impact of NOX4 deficiency on sexually dimorphic lipid handling in HFD-challenged mice. doctoral thesis, Virginia Tech, 2025. https://hdl.handle.net/10919/134998