Prenatal undernutrition and postnatal overnutrition alter thyroid hormone axis function in sheep

Abstract

Mounting evidence led us to hypothesize that i) function of the thyroid hormone (TH) axis can be programed by late gestation undernutrition (LG-UN) and ii) early-postnatal-life overnutrition (EL-ON) exacerbates the fetal impacts on TH axis function. In a 2!2 factorial experiment, 21 twin-bearing sheep were fed one of two diets during late gestation: NORM (fulfilling energy and protein requirements) or LOW (50% of NORM). From day 3 to 6 months after birth (around puberty), the twin lambs were assigned to each their diet: conventional (CONV) or high-carbohydrate, high-fat, where after half the lambs were killed. Remaining sheep (exclusively females) were fed the same moderate diet until 2 years of age (young adults). At 6 months and 2 years of age, fasting challenges were conducted and target tissues were collected at autopsy. LG-UN caused adult hyperthyroidism associated with increased thyroid expression of genes regulating TH synthesis and deiodination. In one or more of the target tissues, liver, cardiac muscle, and longissimus dorsi muscle, gene expressions were increased by LG-UN for TH receptors (THRA and THRB) and deiodinases but were decreased in visceral and subcutaneous adipose tissues. EL-ON increased TH levels in adolescent lambs, but this was reversed after diet correction and not evident in adulthood. We conclude that LG-UN programed TH axis function at the secretory level and differentially in target tissues, which was increasingly manifested with age. Differential TH signaling in adipose vs other tissues may be part of a mechanism whereby fetal malnutrition can predispose for obesity and other metabolic disorders.

Thermal imprinting modifies adult stress and innate immune responsiveness in the teleost sea bream

“…In mammals, the way in which pre-natal or post-natal 'adverse challenges' has an impact on the hypothalamicpituitary-adrenal (HPA) axis is extensively studied and linked with dysfunction during adulthood and associated pathologies (Fahmi et al 2004, Breton 2013, Devlin et al 2013, Johnsen et al 2013 during childhood are proposed to provoke dysfunction in adulthood due to epigenetic mechanisms that lead to persistent changes in the expression of genes such as the glucocorticoid receptor (GR), together with lifelong alterations in DNA methylation and histone 3 lysine 9 (H3K9) acetylation (Zhang et al 2010).…”

Postnatal exposure to a high-carbohydrate diet interferes epigenetically with thyroid hormone receptor induction of the adult male rat skeletal muscle glucose transporter isoform 4 expression

“…Previous investigations involving a high fat diet during the fetal stages of development disrupted the thyroid hormone axis in both sheep [25] and non-human primates [26]. However similar investigations have not been carried out during exposure to modified nutrition during the early postnatal period of development, our present study being the first.…”

Pre- and postnatal nutrition in sheep affects β-cell secretion and hypothalamic control

“…If this is correct, other key regulatory functions of the hypothalamus and pituitary, such as control of appetite and thyroid and reproductive functions, could potentially be programmed in response to adverse exposures during fetal life as well. To support such an assumption, we did, in fact, find strong impacts of prenatal undernutrition (LOW) on food preference (Nielsen et al 2012) and the thyroid axis, where the LOW females became hyperthyroid (Johnsen et al 2013). It is interesting that in this study the LOW offspring during the first few weeks of life, when they were fed ad libitum, actually preferred to ingest the (for a ruminant atypical) high-fat dairy cream over the highstarch maize, suggesting that an increased appetite for a high-fat diet can indeed be programmed during prenatal life.…”