Nox4 mediates metabolic stress responses

Simple item page
dc.contributor.authorSpecht, Kalyn Sloaneen
dc.contributor.committeechairCraige, Siobhanen
dc.contributor.committeememberSchmelz, Eva Mariaen
dc.contributor.committeememberMiller, Francis J.en
dc.contributor.committeememberDavy, Kevin P.en
dc.contributor.committeememberDrake, Joshua Chadwicken
dc.contributor.departmentHuman Nutrition, Foods and Exerciseen
dc.date.accessioned2022-06-09T08:00:22Zen
dc.date.available2022-06-09T08:00:22Zen
dc.date.issued2022-06-08en
dc.description.abstractDeficits in skeletal muscle mitochondrial metabolism are associated with a wide variety of chronic skeletal muscle and metabolic-related diseases, including diabetes and sarcopenia. Even in patients with advanced skeletal muscle-related diseases, exercise is a well-established method to improve skeletal muscle mitochondrial metabolism, culminating in enhanced whole-body metabolism and decreased disease severity. In response to exercise, there is an increase in reactive oxygen species (ROS) production. Historically, ROS were solely considered to drive disease development. However, ROS are also required for physiological adaptation and many questions still remain regarding their downstream pathways. One significant producer of skeletal muscle ROS with exercise is Nadph oxidase 4 (Nox4). Nox4 is unique compared to other Nox members as it predominantly produces hydrogen peroxide (H2O2), an effective signaling molecule. Here we demonstrate an essential role for Nox4 in mediating the beneficial effects of exercise. This work will contribute to our understanding of physiological ROS and their downstream targets by identifying a novel role for Nox4 in exercise adaptation. Further defining the molecular events that promote exercise adaptation will be essential for formulating new treatment strategies for patients with chronic metabolic diseases.en
dc.description.abstractgeneralExercise is a widely effective tool for both preventing and reversing disease. Even patients with advanced skeletal muscle and metabolic-related diseases can benefit from continual and repeated exercise training. While decades of work have supported the effectiveness of exercise as a therapeutic intervention, the mechanistic understanding of what occurs at the cellular level remains incomplete. Here, we elucidate a novel pathway mediating important metabolic adaptations to exercise. In response to exercise stress, reactive oxygen species (ROS) are produced in skeletal muscle. ROS facilitate metabolic adaptations to meet the body's need for increased energy. One significant source of ROS comes from Nadph oxidase 4 (Nox4) which plays an essential role in metabolic regulation. The skeletal muscle metabolic response to stress is largely dependent on adaptations that include changes in gene expression, substrate oxidation, and mitochondrial metabolic adaptations. These mitochondrial adaptations include mitochondrial recycling after exercise in skeletal muscle (referred to as mitophagy). We have shown that Nox4 increases the expression of a subset of metabolic genes, is required for substrate oxidation after exercise, and is important for exercise-induced mitophagy.en
dc.description.degreeDoctor of Philosophyen
dc.format.mediumETDen
dc.identifier.othervt_gsexam:35098en
dc.identifier.urihttp://hdl.handle.net/10919/110495en
dc.language.isoenen
dc.publisherVirginia Techen
dc.rightsIn Copyrighten
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/en
dc.subjectReactive oxygen speciesen
dc.subjectskeletal muscle metabolismen
dc.subjectmitochondriaen
dc.subjectmitophagyen
dc.subjectexercise adaptationen
dc.titleNox4 mediates metabolic stress responsesen
dc.typeDissertationen
thesis.degree.disciplineHuman Nutrition, Foods, and Exerciseen
thesis.degree.grantorVirginia Polytechnic Institute and State Universityen
thesis.degree.leveldoctoralen
thesis.degree.nameDoctor of Philosophyen

Files

Original bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
Specht_KS_D_2022.pdf
Size:
3.45 MB
Format:
Adobe Portable Document Format
Download

Collections

Doctoral Dissertations