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Orally induced hyperthyroidism regulates hypothalamic AMP-Activated Protein kinase



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Capelli, Valentina and Grijota Martínez, Carmen and Dragano, Nathalia R. V and Rial- ensado, Eval and Fernø, Johan and Nogueiras, Rubén and Mittag, Jens and Diéguez, Carlos and López, Miguel (2021) Orally induced hyperthyroidism regulates hypothalamic AMP-Activated Protein kinase. Nutrients, 13 (12). pp. 1-17. ISSN Electronic: 2072-6643

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Official URL: https:// doi.org/10.3390/nu13124204


Besides their direct effects on peripheral metabolic tissues, thyroid hormones (TH) act on the hypothalamus to modulate energy homeostasis. However, since most of the hypothalamic actions of TH have been addressed in studies with direct central administration, the estimation of the relative contribution of the central vs. peripheral effects in physiologic conditions of peripheral release (or administration) of TH remains unclear. In this study we used two different models of peripherally induced hyperthyroidism (i.e., T4 and T3 oral administration) to assess and compare the serum and hypothalamic TH status and relate them to the metabolic effects of the treatment. Peripheral TH treatment affected feeding behavior, overall growth, core body temperature, body composition, brown adipose tissue (BAT) morphology and uncoupling protein 1 (UCP1) levels and metabolic activity, white adipose tissue (WAT) browning and liver metabolism. This resulted in an increased overall uncoupling capacity and a shift of the lipid metabolism from WAT accumulation to BAT fueling. Both peripheral treatment protocols induced significant changes in TH concentrations within the hypothalamus, with T3 eliciting a downregulation of hypothalamic AMP-activated protein kinase (AMPK), supporting the existence of a central action of peripheral TH. Altogether, these data suggest that peripherally administered TH modulate energy balance by various mechanisms; they also provide a unifying vision of the centrally mediated and the direct local metabolic effect of TH in the context of hyperthyroidism.

Item Type:Article
Uncontrolled Keywords:Thyroid hormones; AMPK; Hypothalamus; Brown adipose tissue; Browning
Subjects:Medical sciences > Biology > Molecular biology
Medical sciences > Biology > Biochemistry
Medical sciences > Biology > Neurosciences
ID Code:72895
Deposited On:15 Jun 2022 10:10
Last Modified:15 Jun 2022 11:00

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