4.4 Article

Fasting reduces the number of TRH immunoreactive neurons in the hypothalamic paraventricular nucleus of male rats, but not in mice

期刊

NEUROSCIENCE LETTERS
卷 752, 期 -, 页码 -

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.neulet.2021.135832

关键词

Food restriction; Hypothalamus; Leptin; Thyroid hormones; Weight loss

资金

  1. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP/Brazil) [16/02224-1, 16/20897-3, 17/16473-6, 17/17998-5, 20/013188]
  2. Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq/Brazil) [426378/2016]
  3. Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [17/16473-6] Funding Source: FAPESP

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The study found species-specific differences in the effects of fasting on animals, with a reduction in PVHTRH neurons in rats but not mice, as well as differences in the action of leptin in rats and mice.
During fasting or weight loss, the fall in leptin levels leads to suppression of thyrotropin-releasing hormone (TRH) expression in the paraventricular nucleus of the hypothalamus (PVH) and, consequently, inhibition of the hypothalamic-pituitary-thyroid (HPT) axis. However, differently than rats, just few PVHTRH neurons express the leptin receptor in mice. In the present study, male adult rats and mice were submitted to 48-h fasting to evaluate the consequences on proTRH peptide expression at the PVH level. Additionally, the proTRH peptide expression was also assessed in the brains of leptin-deficient (Lep(ob/ob)) mice. We observed that approximately 50 % of PVHTRH neurons of leptin-injected rats exhibited phosphorylation of the signal transducer and activator of transcription 3 (pSTAT3), a marker of leptin receptor activation. In contrast, very few PVHTRH neurons of leptin-injected mice exhibited pSTAT3. Rats submitted to 48-h fasting showed a significant reduction in the number of PVHTRH immunoreactive neurons, as compared to fed rats. On the other hand, no changes in the number of PVHTRH immunoreactive neurons were observed between fasted and fed mice. Next, the number of TRH immunoreactive cells was determined in the PVH, dorsomedial nucleus of the hypothalamus and nucleus raphe pallidus of Lep(ob/ob) and wild-type mice and no significant differences were observed, despite reduced plasma T4 levels in Lep(ob/ob) mice. Taken together, these findings provide additional evidence of the important species-specific differences in the mechanisms used by fasting and/or leptin to regulate the HPT axis.

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