Maternal obesogenic diet during pregnancy and its impact on fetal hepatic function in baboons

Simple item page
dc.contributor.authorMeakin, A.S.
dc.contributor.authorNathanielsz, P.W.
dc.contributor.authorLi, C.
dc.contributor.authorHuber, H.F.
dc.contributor.authorClifton, V.L.
dc.contributor.authorWiese, M.D.
dc.contributor.authorMorrison, J.L.
dc.date.issued2024
dc.description.abstractObjective: Maternal obesity (MO) increases the risk of later-life liver disease in offspring, especially in males. This may be due to impaired cytochrome P450 (CYP) enzyme activity driven by an altered maternal-fetal hormonal milieu. MO increases fetal cortisol concentrations that may increase CYP activity; however, glucocorticoid receptor (GR)-mediated signaling can be modulated by alternative GR isoform expression. We hypothesized that MO induces sex-specific changes in GR isoform expression and localization that contribute to reduced hepatic CYP activity. Methods: Nonpregnant, nulliparous female baboons were assigned to either an ad libitum control diet or a high-fat, high-energy diet (HF-HED) at 9 months pre pregnancy. At 165 days’ gestation (term = 180 days), fetal liver samples were collected (n = 6/sex/ group). CYP activity was quantified using functional assays, and GR was measured using quantitative RT-PCR and Western blot. Results: CYP3A activity was reduced in the HF-HED group, whereas CYP2B6 activity was reduced in HF-HED males only. Total GR expression was increased in the HF-HED group. Relative nuclear expression of the antagonistic GR isoform GRβ was increased in HF-HED males only. Conclusions: Reduced CYP activity in HF-HED males may be driven in part by dampened hepatic-specific glucocorticoid signaling via altered GR isoform expression. These findings highlight targetable mechanisms that may reduce later-life sex-specific disease risk.
dc.description.statementofresponsibilityAshley S. Meakin, Peter W. Nathanielsz, Cun Li, Hillary F. Huber, Vicki L. Clifton, Michael D. Wiese, Janna L. Morrison
dc.identifier.citationObesity, 2024; 32(10):1910-1922
dc.identifier.doi10.1002/oby.24124
dc.identifier.issn1930-7381
dc.identifier.issn1930-739X
dc.identifier.orcidClifton, V.L. [0000-0002-4892-6748]
dc.identifier.urihttps://hdl.handle.net/2440/143646
dc.language.isoen
dc.publisherWILEY
dc.relation.granthttp://purl.org/au-research/grants/arc/FT170100431
dc.rights© 2024 The Author(s). Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
dc.source.urihttps://doi.org/10.1002/oby.24124
dc.subjectMaternal obesity (MO); later-life liver disease in offspring
dc.subject.meshLiver
dc.subject.meshFetus
dc.subject.meshAnimals
dc.subject.meshPapio
dc.subject.meshPrenatal Exposure Delayed Effects
dc.subject.meshObesity
dc.subject.meshHydrocortisone
dc.subject.meshCytochrome P-450 Enzyme System
dc.subject.meshReceptors, Glucocorticoid
dc.subject.meshPregnancy
dc.subject.meshFemale
dc.subject.meshMale
dc.subject.meshMaternal Nutritional Physiological Phenomena
dc.subject.meshDiet, High-Fat
dc.subject.meshObesity, Maternal
dc.subject.meshPregnancy in Obesity
dc.titleMaternal obesogenic diet during pregnancy and its impact on fetal hepatic function in baboons
dc.typeJournal article
pubs.publication-statusPublished

Files

Original bundle
Now showing 1 - 1 of 1
No Thumbnail Available
Name:
hdl_143646.pdf
Size:
4.18 MB
Format:
Adobe Portable Document Format
Description:
Published version
Download

Collections

Research Outputs