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Fat fetuses: thyroid hormone deficiency before birth modifies adipose tissue development

last modified Mar 06, 2020 10:28 AM
New study by PDN and collaborators demonstrates that thyroid hormone deficiency before birth causes overgrowth of white adipose tissue

Congenital hypothyroidism (lack of thyroid hormones at birth) is the most common congenital endocrine disorder that affects around 1 in 2000 neonates worldwide. Affected infants are at risk of hypothermia and are more likely to become overweight and insulin resistant in childhood and adolescence, even when diagnosed and treated with thyroid hormones soon after birth. Thyroid hormone deficiency is also common in babies born preterm and/or growth restricted and these infants are similarly prone to metabolic dysfunction and obesity in later life. The environment before birth is well known to impact the short and long term health of the offspring, although the molecular mechanisms responsible are less clear.

Harris and colleagues at the Universities of Cambridge, Oxford Brookes and Western Australia have characterised the structure, transcriptome and protein expression of adipose tissue in a sheep model of fetal hypothyroidism. Their study demonstrates that thyroid hormone deficiency before birth causes overgrowth of white adipose tissue and although the amount of brown adipose tissue remained unchanged, its ability to produce heat was reduced. Using RNA-sequencing and genomic analyses, hypothyroidism was shown to affect one-third of the transcriptome in fetal adipose tissue and to change a number of key genes and molecular pathways important for adipogenesis and adipose function, including insulin sensitivity and thermoregulation. Changes to the adipose transcriptome and phenotype observed in the hypothyroid fetus may have consequences for neonatal health and the risk of obesity and metabolic dysfunction in later life.

Eeference: Harris SE, De Blasio MJ, Zhao X, Ma M, Davies K, Wooding FBP, Hamilton RS, Blache D, Meredith D, Murray AJ, Fowden AL, Forhead A (2020) Thyroid deficiency before birth alters the adipose transcriptome to promote overgrowth of white adipose tissue and impair thermogenic capacity. Thyroid doi: 10.1089/thy.2019.0749.

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