Maternal adaptations in mouse lactation are vulnerable to diet-induced excess adiposity

Jessica A. Breznik, Tatiane A. Ribeiro, Erica Yeo, Brianna K. E. Kennelly, Xuanyu Wang, Candice Quin, Braeden Cowbrough, Elena F. Verdú, Dawn M. E. Bowdish, Deborah M. Sloboda

Research output: Working paperPreprint

Abstract

Lifetime maternal risk of obesity is increased by excess gestational weight gain, which alters maternal metabolic adaptations in pregnancy, but the effects of excess weight retention/adiposity in the early postpartum period have not been extensively studied. The pathophysiology of excess adiposity and its accompanying immunometabolic dysregulation are associated with impaired intestinal barrier function in both non-pregnant and pregnant contexts. Using a mouse model, we investigated effects of diet-induced excess adiposity on maternal physiological adaptations during lactation. We report that in lactation, excess adiposity altered maternal intestinal morphology, influenced local immune cell composition and phenotype, increased intestinal permeability, and altered whole-body glucose metabolism as well as peripheral inflammation and immune cell composition. Many of these effects persisted two months post-lactation in mice with excess adiposity. Our findings have important implications for the development of interventions for periconceptual/perinatal excess adiposity and emphasize that further studies are needed to better understand effects of excess adiposity on maternal postpartum health.
Original languageEnglish
PublisherbioRxiv
Number of pages66
DOIs
Publication statusPublished - 23 Jul 2023

Bibliographical note

The authors would like to thank the McMaster University Central Animal Facility staff and veterinarians for their care of the animals in this study, Hong Liang and the McMaster Immunology Research Centre flow cytometry facility, Erin Demask and Tina Walker for provision of media, John Grainger for guidance on intestinal tissue processing and flow cytometry protocol design, and Katherine Kennedy and Patrycja Jazwiec for their assistance with tissue collections. Figures 1 and 10 were made using BioRender.com.

Funding

This work was funded by a Team Grant from the Canadian Institutes of Health Research (CIHR) led by DMS. JAB was supported by a Queen Elizabeth II Scholarship in Science and Technology and McMaster Institute for Research in Aging Postdoctoral Fellowship. TAR was supported by a McMaster Institute for Research on Aging Post-Doctoral Fellowship and M.G. DeGroote Post-Doctoral Fellowship Award. BKEK was supported by a CIHR Canada Graduate Scholarships – Master’s (CGS-M) award. EY was supported by a Farncombe Family Student Scholarship and NSERC CGS-D scholarship. CQ was supported by a CIHR Postdoctoral Fellowship Award. EFV is funded by CIHR grants PJT-168840 and PJT-183881, and holds a Canada Research Chair in Microbial Therapeutics and Nutrition in Gastroenterology. Work in the Bowdish laboratory is supported by the CIHR, McMaster Immunology Research Centre, and the M. G. DeGroote Institute for Infectious Disease Research. DMEB holds a Canada Research Chair in Aging and Immunity. DMS holds a Canada Research Chair in Perinatal Programming.

FundersFunder number
Canadian Institutes of Health ResearchPJT-168840, PJT-183881

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