Lactational metformin exposure programs offspring white adipose tissue glucose homeostasis and resilience to metabolic stress in a sex-dependent manner
| Autor: | Carlson Z, Hannah Hafner, Dave Bridges, Kaylie Bullock, Molly C. Mulcahy, Ernesto Bernal-Mizrachi, Allen Zhu, Brigid Gregg |
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| Rok vydání: | 2020 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty Physiology Offspring Adipose Tissue White Endocrinology Diabetes and Metabolism Adipose tissue 030209 endocrinology & metabolism White adipose tissue Mice 03 medical and health sciences chemistry.chemical_compound Sex Factors 0302 clinical medicine Pregnancy Stress Physiological Physiology (medical) Adipocyte Internal medicine Lactation medicine Animals Homeostasis Hypoglycemic Agents Glucose homeostasis Young adult Cell Proliferation business.industry Metformin Glucose 030104 developmental biology Endocrinology medicine.anatomical_structure chemistry Maternal Exposure Prenatal Exposure Delayed Effects Gestation Female business Research Article medicine.drug |
| Zdroj: | Am J Physiol Endocrinol Metab |
| ISSN: | 1662-4009 |
| DOI: | 10.1530/ey.17.2.16 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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