Liraglutide-Driven Weight Loss Modulates Placental Remodeling in Obese Pregnancies in Mice.

Rodrigo, N; Aksentijevic, D; Patel, N; Pollock, CA; McClements, L; Glastras, SJ

Liraglutide-Driven Weight Loss Modulates Placental Remodeling in Obese Pregnancies in Mice.

Rodrigo, N Aksentijevic, D Patel, N Pollock, CA McClements, L

Glastras, SJ

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Publisher:: MDPI
Publication Type:: Journal Article
Citation:: Cells, 2025, 14, (24), pp. 2009
Issue Date:: 2025-12-17

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Field	Value	Language
dc.contributor.author	Rodrigo, N
dc.contributor.author	Aksentijevic, D
dc.contributor.author	Patel, N
dc.contributor.author	Pollock, CA
dc.contributor.author	McClements, L https://orcid.org/0000-0002-4911-1014
dc.contributor.author	Glastras, SJ
dc.date.accessioned	2026-01-14T00:16:51Z
dc.date.available	2025-12-14
dc.date.available	2026-01-14T00:16:51Z
dc.date.issued	2025-12-17
dc.identifier.citation	Cells, 2025, 14, (24), pp. 2009
dc.identifier.issn	2073-4409
dc.identifier.issn	2073-4409
dc.identifier.uri	http://hdl.handle.net/10453/191771
dc.description.abstract	BACKGROUND: The placenta stands at the maternal-fetal interface and is a key organ regulating the intrauterine environment. In pregnancies exposed to obesity, placental function, signaling, and nutrient handling are adversely altered. Pre-conception weight loss is a potential intervention to alter an obesogenic milieu of pregnancy, which we investigated in a mouse model of maternal obesity using diet or administration of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. METHODS: Pre-pregnancy weight loss in C57BL/6 high-fat diet (HFD)-fed dams was induced in the pre-pregnancy period by switching diet from HFD to chow diet or administering liraglutide (0.3 mg/kg/day subcutaneously for 4 weeks) whilst continuing HFD. In addition, a group of HFD-fed dams were switched to chow diet post-conception. The metabolomic profile and gene expression within the placenta was compared at day 18-20 of gestation. RESULTS: 1H NMR spectroscopy metabolomic analysis of placenta of HFD mice showed an altered amino acid metabolomic profile, with lower aspartate, glutamate, and glutamine levels compared to the placenta of chow-fed mice (p < 0.05). Meanwhile, gene expression analysis identified both oxidative stress and inflammation in the placentas of HFD-fed dams. Whilst dietary modification alone was sufficient to reduce markers of oxidative stress and inflammation, liraglutide treatment modulated pathological changes, including placental metabolic stress but not inflammation. CONCLUSIONS: These findings highlight the importance of dietary or pharmacological interventions in the pre- or immediate post-conception period, with pre-conception offering a critical window to reduce aberrant placental changes induced by obesity.
dc.format	Electronic
dc.language	eng
dc.publisher	MDPI
dc.relation	National Heart Foundation of Australia106628
dc.relation	NATIONAL HEART FOUNDATION OF AUSTRALIA106628
dc.relation.ispartof	Cells
dc.relation.isbasedon	10.3390/cells14242009
dc.rights	info:eu-repo/semantics/openAccess
dc.subject.classification	31 Biological sciences
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.mesh	Animals
dc.subject.mesh	Liraglutide
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	Placenta
dc.subject.mesh	Mice
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Weight Loss
dc.subject.mesh	Diet, High-Fat
dc.subject.mesh	Obesity
dc.subject.mesh	Oxidative Stress
dc.subject.mesh	Pregnancy in Obesity
dc.subject.mesh	Placenta
dc.subject.mesh	Animals
dc.subject.mesh	Mice, Inbred C57BL
dc.subject.mesh	Mice
dc.subject.mesh	Obesity
dc.subject.mesh	Weight Loss
dc.subject.mesh	Oxidative Stress
dc.subject.mesh	Pregnancy
dc.subject.mesh	Female
dc.subject.mesh	Diet, High-Fat
dc.subject.mesh	Liraglutide
dc.subject.mesh	Pregnancy in Obesity
dc.title	Liraglutide-Driven Weight Loss Modulates Placental Remodeling in Obese Pregnancies in Mice.
dc.type	Journal Article
utslib.citation.volume	14
utslib.location.activity	Switzerland
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
pubs.organisational-group	University of Technology Sydney/UTS Groups
pubs.organisational-group	University of Technology Sydney/UTS Groups/Women & Children’s Health Research Collaborative (WCHC)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)
pubs.organisational-group	University of Technology Sydney/UTS Groups/Institute of Biomedical Materials and Devices (IBMD)/Institute of Biomedical Materials and Devices (IBMD) Associate Members
utslib.copyright.status	open_access	*
dc.rights.license	This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/
dc.date.updated	2026-01-14T00:16:49Z
pubs.issue	24
pubs.publication-status	Published online
pubs.volume	14
utslib.citation.issue	24

Abstract:

BACKGROUND: The placenta stands at the maternal-fetal interface and is a key organ regulating the intrauterine environment. In pregnancies exposed to obesity, placental function, signaling, and nutrient handling are adversely altered. Pre-conception weight loss is a potential intervention to alter an obesogenic milieu of pregnancy, which we investigated in a mouse model of maternal obesity using diet or administration of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. METHODS: Pre-pregnancy weight loss in C57BL/6 high-fat diet (HFD)-fed dams was induced in the pre-pregnancy period by switching diet from HFD to chow diet or administering liraglutide (0.3 mg/kg/day subcutaneously for 4 weeks) whilst continuing HFD. In addition, a group of HFD-fed dams were switched to chow diet post-conception. The metabolomic profile and gene expression within the placenta was compared at day 18-20 of gestation. RESULTS: 1H NMR spectroscopy metabolomic analysis of placenta of HFD mice showed an altered amino acid metabolomic profile, with lower aspartate, glutamate, and glutamine levels compared to the placenta of chow-fed mice (p < 0.05). Meanwhile, gene expression analysis identified both oxidative stress and inflammation in the placentas of HFD-fed dams. Whilst dietary modification alone was sufficient to reduce markers of oxidative stress and inflammation, liraglutide treatment modulated pathological changes, including placental metabolic stress but not inflammation. CONCLUSIONS: These findings highlight the importance of dietary or pharmacological interventions in the pre- or immediate post-conception period, with pre-conception offering a critical window to reduce aberrant placental changes induced by obesity.

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http://hdl.handle.net/10453/191771