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

Area of Science:

• Endocrinology
• Developmental programming
• Metabolic disorders

Background:

• Thyroid hormone (TH) axis regulation is crucial for metabolism.
• Maternal nutrition during gestation can impact offspring's long-term health.
• Nutritional challenges in early life may influence endocrine system development.

Purpose of the Study:

• To investigate the programming effects of late gestation undernutrition (LG-UN) on the TH axis.
• To determine if early postnatal overnutrition (EL-ON) exacerbates LG-UN impacts.
• To examine age-dependent changes in TH axis function and tissue-specific responses.

Main Methods:

• A 2x2 factorial study in twin-bearing sheep subjected to normal (NORM) or low (LOW) gestation diets.
• Lambs received conventional (CONV) or high-carbohydrate, high-fat (EL-ON) diets postnatally.
• Fasting challenges and tissue collection at 6 months and 2 years of age.

Main Results:

• LG-UN resulted in adult hyperthyroidism with altered TH synthesis and deiodination gene expression in the thyroid.
• LG-UN increased TH receptor and deiodinase gene expression in liver, heart, and muscle, but decreased it in adipose tissue.
• EL-ON transiently increased TH levels in adolescents, with effects not persisting into adulthood.

Conclusions:

• LG-UN programs TH axis function, affecting both secretion and tissue-specific signaling.
• Differential TH signaling in adipose versus other tissues may link fetal malnutrition to obesity.
• Age-dependent manifestation of programming effects highlights the long-term consequences of developmental nutrition.