Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner

Zach Carlson, Hannah Hafner, Molly Mulcahy, Kaylie Bullock, Allen Zhu, Dave Bridges, Ernesto Bernal-Mizrachi, Brigid Gregg

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

We previously demonstrated that exposing mouse dams to metformin during gestation results in increased beta-cell mass at birth and increased beta-cell insulin secretion in adult male offspring. Given these favorable changes after a gestational maternal metformin exposure, we wanted to understand the long-term metabolic impact on offspring after exposing dams to metformin during the postnatal window. The newborn period provides a feasible clinical window for intervention and is important for beta-cell proliferation and metabolic tissue development. Using a C57BL/6 model, we administered metformin to dams from the day of birth to postnatal day 21. We monitored maternal health and offspring growth during the lactation window, as well as adult glucose homeostasis through in vivo testing. At necropsy we assessed pancreas and adipocyte morphology using histological and immunofluorescent staining techniques. We found that metformin exposure programmed male and female offspring to be leaner with a higher proportion of small adipocytes in the gonadal white adipose tissue (GWAT). Male, but not female, offspring had an improvement in glucose tolerance as young adults concordant with a mild increase in insulin secretion in response to glucose in vivo. These data demonstrate long-term metabolic programming of offspring associated with maternal exposure to metformin during lactation.

Original languageEnglish (US)
Pages (from-to)E600-E612
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume318
Issue number5
DOIs
StatePublished - May 2020

Keywords

  • Adipose
  • Developmental programming
  • Lactation
  • Metformin
  • Neonatal

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)

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