@article{5690e9aa4f2e421c90c7c2a323d26eba,
title = "Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner",
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.",
keywords = "Adipose, Developmental programming, Lactation, Metformin, Neonatal",
author = "Zach Carlson and Hannah Hafner and Molly Mulcahy and Kaylie Bullock and Allen Zhu and Dave Bridges and Ernesto Bernal-Mizrachi and Brigid Gregg",
note = "Funding Information: We acknowledge the White Adipose Tissue Core, which is a part of the Michigan Nutrition and Obesity Center [under National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant P30-DK-089503] for instruction in adipocyte size analysis. Body composition measurements and metabolic caging experiments were done with the assistance of the Mouse Metabolic Phenotyping Center (under NIDDK Grant U2C-DK-110768). B.G. is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant K08-DK-102526 and the Amendt-Heller Award for Newborn Research. D.B. is supported by NIDDK Grant R01-DK-107535. E.B.M. is supported by NIDDK R01-DK-084236. Metformin levels were analyzed at the Michigan Regional Comprehensive Metabolomics Resource Core (MRC2) supported by NIDDK Grant DK-097153 to the University of Michigan. B.G. was also supported by the Amendt-Heller Award for Newborn Research and a Michigan Diabetes Research Center Pilot and Feasibility Grant (NIDDK Grant 2P30-DK020572). Z.C. was funded by an internship through the Momentum Center of the University of Michigan. M.M. was supported by a Rackham Merit Fellowship, University of Michigan. Funding Information: B.G. is supported by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) Grant K08-DK-102526 and the Amendt-Heller Award for Newborn Research. D.B. is supported by NIDDK Grant R01-DK-107535. E.B.M. is supported by NIDDK R01-DK-084236. Metformin levels were analyzed at the Michigan Regional Comprehensive Metabolomics Resource Core (MRC2) supported by NIDDK Grant DK-097153 to the University of Michigan. B.G. was also supported by the Amendt-Heller Award for Newborn Research and a Michigan Diabetes Research Center Pilot and Feasibility Grant (NIDDK Grant 2P30-DK020572). Z.C. was funded by an internship through the Momentum Center of the University of Michigan. M.M. was supported by a Rackham Merit Fellowship, University of Michigan. Publisher Copyright: {\textcopyright} 2020 the American Physiological Society Copyright: Copyright 2020 Elsevier B.V., All rights reserved.",
year = "2020",
month = may,
doi = "10.1152/ajpendo.00473.2019",
language = "English (US)",
volume = "318",
pages = "E600--E612",
journal = "American Journal of Physiology - Cell Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "5",
}