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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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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