RT Journal Article
T1 Orally induced hyperthyroidism regulates hypothalamicAMP-Activated Protein kinase
A1 Capelli, Valentina
A1 Grijota Martínez, Carmen
A1 Dragano, Nathalia R. V
A1 Rial-Pensado, Eva
A1 Fernø, Johan
A1 Nogueiras, Rubén
A1 Mittag, Jens
A1 Diéguez, Carlos
A1 López, Miguel
AB 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.
PB MDPI
SN 2072-6643
YR 2021
FD 2021
LK https://hdl.handle.net/20.500.14352/4938
UL https://hdl.handle.net/20.500.14352/4938
LA eng
NO European Commission
NO Ministerio de Economía y Competitividad (España)
NO Xunta de Galicia
NO Fundación “la Caixa"
NO European Foundation for the Study of Diabetes
NO Deutsche Forschungsgemeinschaft
NO Western Norway Regional Health Authority
NO Fundación BBVA
NO Atresmedia Corporación
DS Docta Complutense
RD 13 dic 2025