Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight

The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thy...

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Main Authors: Saira Hameed, Michael Patterson, Waljit S. Dhillo, Sofia A. Rahman, Yue Ma, Christopher Holton, Apostolos Gogakos, Giles S.H. Yeo, Brian Y.H. Lam, Joseph Polex-Wolf, Wiebke Fenske, Jimmy Bell, Jelena Anastasovska, Jacques Samarut, Stephen R. Bloom, J.H. Duncan Bassett, Graham R. Williams, James V. Gardiner
Format: Article
Language:English
Published: Elsevier 2017-06-01
Series:Cell Reports
Subjects:
thyroid hormone
thyroid hormone receptor beta
hypothalamus
ventromedial hypothalamus
VMH
body weight
obesity
food intake
appetite
energy expenditure
Online Access:http://www.sciencedirect.com/science/article/pii/S2211124717307234
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spelling doaj-d368c488aef54187b714d5c151f12af62020-11-25T02:08:40ZengElsevierCell Reports2211-12472017-06-0119112202220910.1016/j.celrep.2017.05.066Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body WeightSaira Hameed0Michael Patterson1Waljit S. Dhillo2Sofia A. Rahman3Yue Ma4Christopher Holton5Apostolos Gogakos6Giles S.H. Yeo7Brian Y.H. Lam8Joseph Polex-Wolf9Wiebke Fenske10Jimmy Bell11Jelena Anastasovska12Jacques Samarut13Stephen R. Bloom14J.H. Duncan Bassett15Graham R. Williams16James V. Gardiner17Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKMolecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UKSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKMolecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UKUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UKUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UKUniversity of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UKSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKMetabolic and Molecular Imaging Group, Imperial College London, London W12 0NN, UKMetabolic and Molecular Imaging Group, Imperial College London, London W12 0NN, UKInstitut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, 69364 Lyon, FranceSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKMolecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UKMolecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UKSection of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UKThe obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs), which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.http://www.sciencedirect.com/science/article/pii/S2211124717307234thyroid hormonethyroid hormone receptor betahypothalamusventromedial hypothalamusVMHbody weightobesityfood intakeappetiteenergy expenditure
collection DOAJ
language English
format Article
sources DOAJ
author Saira Hameed
Michael Patterson
Waljit S. Dhillo
Sofia A. Rahman
Yue Ma
Christopher Holton
Apostolos Gogakos
Giles S.H. Yeo
Brian Y.H. Lam
Joseph Polex-Wolf
Wiebke Fenske
Jimmy Bell
Jelena Anastasovska
Jacques Samarut
Stephen R. Bloom
J.H. Duncan Bassett
Graham R. Williams
James V. Gardiner
spellingShingle Saira Hameed
Michael Patterson
Waljit S. Dhillo
Sofia A. Rahman
Yue Ma
Christopher Holton
Apostolos Gogakos
Giles S.H. Yeo
Brian Y.H. Lam
Joseph Polex-Wolf
Wiebke Fenske
Jimmy Bell
Jelena Anastasovska
Jacques Samarut
Stephen R. Bloom
J.H. Duncan Bassett
Graham R. Williams
James V. Gardiner
Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
Cell Reports
thyroid hormone
thyroid hormone receptor beta
hypothalamus
ventromedial hypothalamus
VMH
body weight
obesity
food intake
appetite
energy expenditure
author_facet Saira Hameed
Michael Patterson
Waljit S. Dhillo
Sofia A. Rahman
Yue Ma
Christopher Holton
Apostolos Gogakos
Giles S.H. Yeo
Brian Y.H. Lam
Joseph Polex-Wolf
Wiebke Fenske
Jimmy Bell
Jelena Anastasovska
Jacques Samarut
Stephen R. Bloom
J.H. Duncan Bassett
Graham R. Williams
James V. Gardiner
author_sort Saira Hameed
title Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
title_short Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
title_full Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
title_fullStr Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
title_full_unstemmed Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
title_sort thyroid hormone receptor beta in the ventromedial hypothalamus is essential for the physiological regulation of food intake and body weight
publisher Elsevier
series Cell Reports
issn 2211-1247
publishDate 2017-06-01
description The obesity epidemic is a significant global health issue. Improved understanding of the mechanisms that regulate appetite and body weight will provide the rationale for the design of anti-obesity therapies. Thyroid hormones play a key role in metabolic homeostasis through their interaction with thyroid hormone receptors (TRs), which function as ligand-inducible transcription factors. The TR-beta isoform (TRβ) is expressed in the ventromedial hypothalamus (VMH), a brain area important for control of energy homeostasis. Here, we report that selective knockdown of TRβ in the VMH of adult mice results in severe obesity due to hyperphagia and reduced energy expenditure. The observed increase in body weight is of a similar magnitude to murine models of the most extreme forms of monogenic obesity. These data identify TRβ in the VMH as a major physiological regulator of food intake and energy homeostasis.
topic thyroid hormone
thyroid hormone receptor beta
hypothalamus
ventromedial hypothalamus
VMH
body weight
obesity
food intake
appetite
energy expenditure
url http://www.sciencedirect.com/science/article/pii/S2211124717307234
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