Thyroid Hormone Receptor Beta in the Ventromedial Hypothalamus Is Essential for the Physiological Regulation of Food Intake and Body Weight
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
Affiliations
Saira Hameed
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
Michael Patterson
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
Waljit S. Dhillo
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
Sofia A. Rahman
Molecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UK
Yue Ma
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
Christopher Holton
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
Apostolos Gogakos
Molecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UK
Giles S.H. Yeo
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
Brian Y.H. Lam
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
Joseph Polex-Wolf
University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK
Wiebke Fenske
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
Jimmy Bell
Metabolic and Molecular Imaging Group, Imperial College London, London W12 0NN, UK
Jelena Anastasovska
Metabolic and Molecular Imaging Group, Imperial College London, London W12 0NN, UK
Jacques Samarut
Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, 69364 Lyon, France
Stephen R. Bloom
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
J.H. Duncan Bassett
Molecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UK
Graham R. Williams
Molecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UK
James V. Gardiner
Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK
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.
