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

American Journal of Physiology. Endocrinology and Metabolism
Zach CarlsonBrigid Gregg

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 gluc...Continue Reading

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Citations

Oct 20, 2020·Experimental Physiology·Carina PreviateClaudinéia Conationi da Silva Franco

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Methods Mentioned

BETA
NMR
ELISA
nuclear magnetic resonance

Software Mentioned

MassHunter
lme4
MetaMorph
ImageJ2
GraphPad
GraphPad Prism
ImageJ

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