Mounting evidence led us to hypothesize that: 1) function of the thyroid hormone (TH) axis can be programmed by late-gestation undernutrition (LG-UN), and 2) 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 (HCHF), where after half the lambs were slaughtered. 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 programmed TH-axis function at the secretory level and differentially in target tissues, which was increasingly manifested with age. Differential TH signaling in adipose versus other tissues may be part of a mechanism whereby fetal malnutrition can predispose for obesity and other metabolic disorders.
Journal of Endocrinology, 2013, Vol 216, Issue 3, p. 389-402