Ablation of PI3K-p110alpha impairs maternal metabolic adaptations to pregnancy
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Authors
Lopez Tello, Jorge
Salazar-Petres, Esteban
Webb, Liam
Fowden, Abigail L
Sferruzzi-Perri, Amanda
Journal Title
Frontiers in Cell and Developmental Biology
ISSN
2296-634X
Publisher
Frontiers Media
Type
Article
This Version
AM
Metadata
Show full item recordCitation
Lopez Tello, J., Salazar-Petres, E., Webb, L., Fowden, A. L., & Sferruzzi-Perri, A. Ablation of PI3K-p110alpha impairs maternal metabolic adaptations to pregnancy. Frontiers in Cell and Developmental Biology https://doi.org/10.17863/CAM.85421
Abstract
Pregnancy requires adaptations in maternal metabolism to support fetal growth. The phosphoinositol-3-kinase (PI3K) signalling
pathway controls multiple biological processes and defects in this pathway are linked to metabolic disorders including insulin
resistance and glucose intolerance in non-pregnant animals. However, relatively little is known about the contribution of PI3K
signalling to the maternal metabolic adaptations during pregnancy. Using mice with partial inactivation of the PI3K isoform, p110α
(due to a heterozygous dominant negative mutation; Pik3ca‐D933A), the effects of impaired PI3K‐p110α signalling on glucose and
insulin handling were examined in the pregnant and non-pregnant states and related to the morphological, molecular, and
mitochondrial changes in key metabolic organs. The results show that non‐pregnant mice lacking PI3K‐p110α are glucose intolerant
but exhibit compensatory increases in pancreatic glucose-stimulated insulin release and adipose tissue mitochondrial respiratory
capacity and fatty acid oxidation. However, in pregnancy, mutant mice failed to show the normal increment in glucose intolerance
and pancreatic β‐cell mass observed in wild‐type pregnant dams and exhibited further enhanced adipose tissue mitochondrial
respiratory capacity. These maladaptations in pregnant mutant mice were associated with fetal growth restriction. Hence,
PI3K‐p110α is a key regulator of metabolic adaptations that support fetal growth during normal pregnancy.
Sponsorship
JL-T holds a Sir Henry Wellcome Postdoctoral Fellowship (220456/Z/20/Z). ESP was supported by a Beca-Chile, ANID Postdoctoral Scholarship: 57774190055. ANSP is supported by a MRC New Investigator Grant (MR/R022690/1 / RG93186) and Lister Institute of Preventative Medicine Research Prize (RG93692).
Funder references
Wellcome Trust (220456/Z/20/Z)
Embargo Lift Date
2025-06-10
Identifiers
This record's DOI: https://doi.org/10.17863/CAM.85421
This record's URL: https://www.repository.cam.ac.uk/handle/1810/338016
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