Hypothalamic AMPK and Fatty Acid Metabolism Mediate Thyroid Regulation of Energy Balance

Overview

Journal Nat Med

Specialties General Medicine
Molecular Biology

Date 2010 Aug 31

PMID 20802499

Citations 292

Authors

Miguel Lopez

Luis Varela

Maria J Vazquez

Sergio Rodriguez-Cuenca

Carmen R Gonzalez

Vidya R Velagapudi

Donald A Morgan

Erik Schoenmakers

Khristofor Agassandian

Ricardo Lage

Pablo Blanco Martinez de Morentin

Sulay Tovar

Ruben Nogueiras

David Carling

Christopher Lelliott

Rosalia Gallego

Matej Oresic

Krishna Chatterjee

Asish K Saha

Kamal Rahmouni

Carlos Dieguez

Antonio Vidal-Puig

Affiliations

Soon will be listed here.

Abstract

Thyroid hormones have widespread cellular effects; however it is unclear whether their effects on the central nervous system (CNS) contribute to global energy balance. Here we demonstrate that either whole-body hyperthyroidism or central administration of triiodothyronine (T3) decreases the activity of hypothalamic AMP-activated protein kinase (AMPK), increases sympathetic nervous system (SNS) activity and upregulates thermogenic markers in brown adipose tissue (BAT). Inhibition of the lipogenic pathway in the ventromedial nucleus of the hypothalamus (VMH) prevents CNS-mediated activation of BAT by thyroid hormone and reverses the weight loss associated with hyperthyroidism. Similarly, inhibition of thyroid hormone receptors in the VMH reverses the weight loss associated with hyperthyroidism. This regulatory mechanism depends on AMPK inactivation, as genetic inhibition of this enzyme in the VMH of euthyroid rats induces feeding-independent weight loss and increases expression of thermogenic markers in BAT. These effects are reversed by pharmacological blockade of the SNS. Thus, thyroid hormone-induced modulation of AMPK activity and lipid metabolism in the hypothalamus is a major regulator of whole-body energy homeostasis.

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