Orally induced hyperthyroidism regulates hypothalamic amp-activated protein kinase

Valentina Capelli; Carmen Grijota-Martínez; Nathalia R.V. Dragano; Eval Rial-Pensado; Johan Fernø; Rubén Nogueiras; Jens Mittag; Carlos Diéguez; Miguel López

doi:10.3390/nu13124204

Orally induced hyperthyroidism regulates hypothalamic amp-activated protein kinase

Valentina Capelli, Carmen Grijota-Martínez, Nathalia R.V. Dragano, Eval Rial-Pensado, Johan Fernø, Rubén Nogueiras, Jens Mittag, Carlos Diéguez, Miguel López^*

^*Corresponding author for this work

5 Citations (Scopus)

Abstract

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.

Original language	English
Article number	4204
Journal	Nutrients
Volume	13
Issue number	12
DOIs	https://doi.org/10.3390/nu13124204
Publication status	Published - 12.2021

Funding

Funding: The research leading to these results has received funding from the Xunta de Galicia (R.N.: 2016-PG057; M.L.: 2016-PG068); Ministerio de Economía y Competitividad (MINECO) co-funded by the FEDER Program of EU (R.N.: RTI2018-099413-B-I00; C.D.: BFU2017-87721-P; M.L.: RTI2018-101840-B-I00); Atresmedia Corporación (R.N. and M.L.); Fundación BBVA (R.N.); la Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160022 (M.L.); European Foundation for the Study of Diabetes (R.N.); ERC Synergy Grant-2019-WATCH-810331 (R.N.), the German Research Foundation DFG (J.M.: MI1242/3-2) and Western Norway Regional Health Authority (Helse Vest RHF) (J.F.). The CiMUS is supported by the Xunta de Galicia (2016–2019, ED431G/05). CIBER de Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The research leading to these results has received funding from the Xunta de Galicia (R.N.: 2016-PG057; M.L.: 2016-PG068); Ministerio de Econom?a y Competitividad (MINECO) co-funded by the FEDER Program of EU (R.N.: RTI2018-099413-B-I00; C.D.: BFU2017-87721-P; M.L.: RTI2018-101840-B-I00); Atresmedia Corporaci?n (R.N. and M.L.); Fundaci?n BBVA (R.N.); la Caixa Foundation (ID 100010434), under the agreement LCF/PR/HR19/52160022 (M.L.); European Foundation for the Study of Diabetes (R.N.); ERC Synergy Grant-2019-WATCH-810331 (R.N.), the German Research Foundation DFG (J.M.: MI1242/3-2) and Western Norway Regional Health Authority (Helse Vest RHF) (J.F.). The CiMUS is supported by the Xunta de Galicia (2016?2019, ED431G/05). CIBER de Fisiopatolog?a de la Obesidad y Nutrici?n is an initiative of ISCIII. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Research Areas and Centers

Academic Focus: Center for Brain, Behavior and Metabolism (CBBM)

DFG Research Classification Scheme

2.22-17 Endocrinology, Diabetology, Metabolism

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.3390/nu13124204

Cite this

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title = "Orally induced hyperthyroidism regulates hypothalamic amp-activated protein kinase",

abstract = "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.",

author = "Valentina Capelli and Carmen Grijota-Mart{\'i}nez and Dragano, \{Nathalia R.V.\} and Eval Rial-Pensado and Johan Fern{\o} and Rub{\'e}n Nogueiras and Jens Mittag and Carlos Di{\'e}guez and Miguel L{\'o}pez",

note = "Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",

year = "2021",

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doi = "10.3390/nu13124204",

language = "English",

volume = "13",

journal = "Nutrients",

issn = "2072-6643",

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T1 - Orally induced hyperthyroidism regulates hypothalamic amp-activated protein kinase

AU - Capelli, Valentina

AU - Grijota-Martínez, Carmen

AU - Dragano, Nathalia R.V.

AU - Rial-Pensado, Eval

AU - Fernø, Johan

AU - Nogueiras, Rubén

AU - Mittag, Jens

AU - Diéguez, Carlos

AU - López, Miguel

PY - 2021/12

Y1 - 2021/12

N2 - 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.

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.

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DO - 10.3390/nu13124204

M3 - Journal articles

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VL - 13

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JF - Nutrients

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Orally induced hyperthyroidism regulates hypothalamic amp-activated protein kinase

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

CRC/TRR 296 LocoTact: Local control of TH action

Cite this

Orally induced hyperthyroidism regulates hypothalamic amp-activated protein kinase

Abstract

Funding

Research Areas and Centers

DFG Research Classification Scheme

UN SDGs

Access to Document

Other files and links

Fingerprint

Projects

CRC/TRR 296 LocoTact: Local control of TH action

Cite this