title: Postnatal early overnutrition changes the leptin signalling pathway in the hypothalamic-pituitary-thyroid axis of young and adult rats.
abstract: Postnatal early overnutrition (EO) is a risk factor for obesity in adult life. Rats raised in a small litter can develop hyperinsulinaemia, hyperphagia, hyperleptinaemia and hypertension as adults. Since leptin regulates the hypothalamic-pituitary-thyroid axis and the metabolism of thyroid hormones, we studied the leptin signalling pathway in pituitary and thyroid glands of the postnatal EO model. To induce EO, at the third day of lactation the litter size was reduced to three pups per litter (SL group). In control litters (NL group), the litter size was adjusted to 10 pups per litter. Body weight and food intake were monitored. Rat offspring were killed at 21 (weaning) and 180 days old (adulthood). Plasma thyroid hormones, thyroid-stimulating hormone (TSH) and leptin were measured by radioimmunoassay. Proteins of the leptin signalling pathway were analysed by Western blotting. Body weight of offspring in the SL group was higher from the seventh day of lactation (+33%, P < 0.05) until 180 days old (+18%, P < 0.05). Offspring in the SL group showed higher visceral fat mass at 21 and 180 days old (+176 and +52%, respectively, P < 0.05), but plasma leptin was higher only at 21 days (+88%, P < 0.05). The SL offspring showed higher plasma TSH, 3,5,3'-triiodothronine (T(3)) and thyroxine (T(4)) at 21 days (+60, +91 and +68%, respectively, P < 0.05), while the opposite was observed at 180 days regarding thyroid hormones (T(3), -10%; and T(4), -30%, P < 0.05), with no difference in TSH levels. In hypothalamus, no change was observed in the leptin signalling pathway at 21 days. However, lower janus thyrosine kinase 2 (JAK2) and phosphorilated-signal transducer and activator of transcription-3 (p-STAT3) content were detected in adulthood. In pituitary, the SL group presented higher leptin receptors (Ob-R), JAK2 and p-STAT3 content at 21 days and lower JAK2 and STAT3 content at 180 days old. In contrast, in thyroid, the Ob-R expression was lower in young SL rats, while the adult SL group presented higher Ob-R and JAK2 content. We showed that postnatal EO induces short- and long-term effects upon the hypothalamic-pituitary-thyroid axis. These changes may help to explain future development of metabolic and endocrine dysfunctions, such as metabolic syndrome and hypothyroidism.
authors.affiliation: Departamento de Ciências Fisiológicas, Instituto de Biologia Roberto Alcantara Gomes, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Ananda Lages
authors.initials: AL
authors.lastname: Rodrigues
authors.forename: Egberto Gaspar
authors.initials: EG
authors.lastname: de Moura
authors.forename: Magna Cottini Fonseca
authors.initials: MC
authors.lastname: Passos
authors.forename: Sheila Cristina Potente
authors.initials: SC
authors.lastname: Dutra
authors.forename: Patricia Cristina
authors.initials: PC
authors.lastname: Lisboa
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism*; D000824:Animal Nutritional Physiological Phenomena; D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D001835:Body Weight; D004435:Eating; D005260:Female; D006963:Hyperphagia / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism* / Q000503:physiopathology; D050152:Intra-Abdominal Fat / Q000254:growth & development / Q000378:metabolism; D053614:Janus Kinase 2 / Q000378:metabolism; D007774:Lactation; D020738:Leptin / Q000097:blood*; D008098:Litter Size; D008297:Male; D009765:Obesity / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D044343:Overnutrition / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D010766:Phosphorylation; D011863:Radioimmunoassay; D051381:Rats; D017208:Rats, Wistar; D054411:Receptors, Leptin / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction; D013961:Thyroid Gland / Q000378:metabolism* / Q000503:physiopathology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
chemical_list: D020738:Leptin; D054411:Receptors, Leptin; D050796:STAT3 Transcription Factor; C494088:Stat3 protein, rat; D014284:Triiodothyronine; D013972:Thyrotropin; C507927:Jak2 protein, rat; D053614:Janus Kinase 2; D013974:Thyroxine