title: Postnatal overnutrition programs the thyroid hormone metabolism and function in adulthood.
abstract: Early overnutrition (EO) during lactation leads to obesity, leptin resistance and lower thyroid hormone (TH) levels during adulthood. To better understand the biological significance of this thyroid hypofunction, we studied the long-term effects of postnatal EO on both the function of hypothalamic-pituitary-thyroid (HPT) axis and the metabolism and action of TH. To induce EO, the litter size was reduced to three pups per litter (small litter (SL) group) on the third day of lactation. In the controls (normal litter group), litter size was adjusted to 10 pups per litter. Rats were killed at PN180. TRH content and in vitro TSH were evaluated. Iodothyronine deiodinase (D1 and D2) activities were measured in different tissues. Mitochondrial α-glycerol-3-phosphate dehydrogenase (mGPD), uncoupling protein 1 (UCP1) and TH receptor (TRβ1) were evaluated to assess TH action. The SL group presented lower TRH, intra-pituitary and released TSH levels, despite unchanged plasma TSH. They presented lower D1 activity in thyroid, muscle and white adipose tissue (WAT) and higher D2 activity in the hypothalamus, pituitary, brown adipose tissue (BAT) and WAT, which confirmed the hypothyroidism. UCP1 in BAT and TRβ1 in WAT were decreased, which can contribute to a lower catabolic status. Despite the lower TH, the D2 activity in the thyroid, heart and testes was unchanged. Hepatic D1, mGPD and TRβ1 were also unchanged in SL rats, suggesting that the TH conversion and action were preserved in the liver, even with lower TH. Thus, this model indicates that postnatal EO changes thyroid function in adult life in a tissue-specific way, which can help in the understanding of obesogenesis.
authors.affiliation: Laboratory of Endocrine PhysiologyDepartment of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Avenida 28 de setembro, 87, Rio de Janeiro, RJ 20551-031, Brazil pclisboa@uerj.br.
authors.forename: Patricia C
authors.initials: PC
authors.lastname: Lisboa
authors.affiliation: Laboratory of Endocrine PhysiologyDepartment of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Avenida 28 de setembro, 87, Rio de Janeiro, RJ 20551-031, Brazil.
authors.forename: Ellen P S
authors.initials: EP
authors.lastname: Conceição
authors.affiliation: Laboratory of Endocrine PhysiologyDepartment of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Avenida 28 de setembro, 87, Rio de Janeiro, RJ 20551-031, Brazil.
authors.forename: Elaine
authors.initials: E
authors.lastname: de Oliveira
authors.affiliation: Laboratory of Endocrine PhysiologyDepartment of Physiological Sciences, Roberto Alcantara Gomes Biology Institute, State University of Rio de Janeiro, Avenida 28 de setembro, 87, Rio de Janeiro, RJ 20551-031, Brazil.
authors.forename: Egberto G
authors.initials: EG
authors.lastname: Moura
mesh_terms: D000818:Animals; D005260:Female; D005993:Glycerolphosphate Dehydrogenase / Q000378:metabolism; D007031:Hypothalamus / Q000378:metabolism; D007037:Hypothyroidism / Q000209:etiology / Q000378:metabolism*; D007453:Iodide Peroxidase / Q000378:metabolism; D007774:Lactation / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism*; D044343:Overnutrition / Q000150:complications / Q000378:metabolism*; D010902:Pituitary Gland / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013961:Thyroid Gland / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism*
chemical_list: D013963:Thyroid Hormones; D005993:Glycerolphosphate Dehydrogenase; D007453:Iodide Peroxidase
keywords: deiodinase; hypothyroidism; lactation; overnutrition; programming