Maternal hypothyroidism in mice influences glucose metabolism in adult offspring

Author(s)

Kemkem, Yasmine ^[1] ; Nasteska, Daniela ^{[2, 3, 4, 5]} ; de Bray, Anne ^{[2, 3, 4, 5]} ; Bargi-Souza, Paula ^[6] ; Peliciari-Garcia, Rodrigo A. ^[7] ; Guillou, Anne ^[1] ; Mollard, Patrice ^[1] ; Hodson, David J. ^{[2, 3, 4, 5]} ; Schaeffer, Marie ^[1]

Affiliation

^[1] Univ Montpellier, Inst Funct Genom, CNRS, Inserm U1191, F-34094 Montpellier - France

^[2] Univ Nottingham, Nottingham - England

^[3] Univ Birmingham, Inst Metab & Syst Res, Edgbaston - England

^[4] Univ Birmingham, COMPARE, Nottingham - England

^[5] Birmingham Hlth Partners, Ctr Endocrinol Diabet & Metab, Birmingham, W Midlands - England

^[6] Univ Fed Minas Gerais, Inst Biol Sci, Dept Physiol & Biophys, Belo Horizonte, MG - Brazil

^[7] Univ Fed Sao Paulo, Dept Biol Sci, Morphophysiol & Pathol Sect, Diadema, SP - Brazil

• Document type: Journal article
• Source: Diabetologia; v. 63, n. 9, p. 1822-1835, SEP 2020.
• Web of Science Citations: 1

Abstract

Aims/hypothesis During pregnancy, maternal metabolic disease and hormonal imbalance may alter fetal beta cell development and/or proliferation, thus leading to an increased risk for developing type 2 diabetes in adulthood. Although thyroid hormones play an important role in fetal endocrine pancreas development, the impact of maternal hypothyroidism on glucose homeostasis in adult offspring remains poorly understood. Methods We investigated this using a mouse model of hypothyroidism, induced by administration of an iodine-deficient diet supplemented with propylthiouracil during gestation. Results Here, we show that, when fed normal chow, adult mice born to hypothyroid mothers were more glucose-tolerant due to beta cell hyperproliferation (two- to threefold increase in Ki67-positive beta cells) and increased insulin sensitivity. However, following 8 weeks of high-fat feeding, these offspring gained 20% more body weight, became profoundly hyperinsulinaemic (with a 50% increase in fasting insulin concentration), insulin-resistant and glucose-intolerant compared with controls from euthyroid mothers. Furthermore, altered glucose metabolism was maintained in a second generation of animals. Conclusions/interpretation Therefore, gestational hypothyroidism induces long-term alterations in endocrine pancreas function, which may have implications for type 2 diabetes prevention in affected individuals. (AU)

• FAPESP's process: 16/24941-7 - Interaction between thyroid hormones and circadian clock genes: consequences on anterior pituitary hormones secretion
• Grantee: Paula Bargi de Souza
• Support Opportunities: Scholarships abroad - Research Internship - Post-doctor