The role of Arginyltransferase 1 in body weight homeostasis

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dc.contributor.advisorBrower, Christopher
dc.contributor.committeeMemberConrad-Webb, Heather
dc.contributor.committeeMemberMills, Nathaniel
dc.contributor.committeeMemberAveritt, Dayna L
dc.contributor.committeeMemberNa, Elisa
dc.creatorAlkhatatbeh, Mosleh Ahmed 1977-
dc.creator.orcid0000-0003-4836-7437
dc.date.accessioned2024-01-12T15:25:14Z
dc.date.created2023-08
dc.date.issuedAugust 2023
dc.date.submittedAugust 2023
dc.date.updated2024-01-12T15:25:15Z
dc.description.abstractPrevious studies reported that systemic deletion of Arginyltransferase 1 (ATE1) in mice results in dramatic fat loss and resistance to diet-induced obesity. However, the mechanisms through which ATE1 influence energy metabolism remain unclear. Here, we investigated the hypothalamic role of ATE1 by examining the effects of the anorectic hormone leptin in wild type (WT) and ATE1-knockout (ATE1-KO) mice maintained on a normal chow diet, or a high fat diet. We found that on both diets, ATE1-KO mice weighed significantly less than WT mice despite consuming more food (hyperphagia). We also found that, similar to WT mice on normal chow, ATE1-KO mice remain responsive to leptin on NC. However, ATE1-KO mice had significantly lower circulating plasma leptin than wild type mice on both diets. This explains (at least in part) their hyperphagia. Interestingly, we also found that leptin reduces the expression of ATE1 in the hypothalamus, indicating that decreased ATE1 activity may be a component of the Leptin regulatory network driving a lean phenotype. In contrast to normal chow, we found that ATE1-KO mice became leptin resistant on high fat diet. Remarkably, we found that the loss of Ate1 gene function reverses high fat diet-induced obesity. Collectively, these results strongly suggest that the inhibition of ATE1 may offer an effective therapeutic strategy to combat obesity.
dc.format.mimetypeapplication/pdf
dc.identifier.uri
dc.identifier.urihttps://hdl.handle.net/11274/15613
dc.language.isoEnglish
dc.subjectArginyltransferase 1; ATE1; obesity; fat loss
dc.subject.otherATE1
dc.subject.otherFat loss
dc.subject.otherDiet-induced obesity
dc.subject.otherObesity
dc.subject.otherEnergy
dc.subject.otherMetabolism
dc.subject.otherHypothalamus
dc.subject.otherAnorectic
dc.subject.otherLeptin
dc.subject.otherATE1-knockout
dc.subject.otherMice
dc.subject.otherNormal chow
dc.subject.otherHigh fat diet
dc.subject.otherArginyltransferase 1
dc.titleThe role of Arginyltransferase 1 in body weight homeostasis
dc.typeThesis
dc.type.materialtext
local.embargo.lift2026-08-01
local.embargo.terms2026-08-01
thesis.degree.collegeCollege of Arts and Sciences
thesis.degree.departmentSchool of the Sciences
thesis.degree.disciplineMolecular Biology
thesis.degree.grantorTexas Woman's University
thesis.degree.nameDoctor of Philosophy
thesis.degree.programAPA 7th edition

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