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

Cell Reports

Jacques Samarut¹  Jelena Anastasovska²  Jimmy Bell²  J.H. Duncan Bassett³  Sofia A. Rahman³  Graham R. Williams³  Apostolos Gogakos³  Stephen R. Bloom⁴  James V. Gardiner⁴  Waljit S. Dhillo⁴  Yue Ma⁴  Michael Patterson⁴  Saira Hameed⁴  Christopher Holton⁴  Wiebke Fenske⁴  Giles S.H. Yeo⁵  Brian Y.H. Lam⁵  Joseph Polex-Wolf⁵ 

[1] Institut de Génomique Fonctionnelle de Lyon, Ecole Normale Supérieure de Lyon, 69364 Lyon, France;Metabolic and Molecular Imaging Group, Imperial College London, London W12 0NN, UK;Molecular Endocrinology Laboratory, Hammersmith Campus, Imperial College London, London W12 0NN, UK;Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London W12 0NN, UK;University of Cambridge Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke’s Hospital, Cambridge CB2 0QQ, UK;

关键词: thyroid hormone;    thyroid hormone receptor beta;    hypothalamus;    ventromedial hypothalamus;    VMH;    body weight;    obesity;    food intake;    appetite;    energy expenditure;   

DOI  :  10.1016/j.celrep.2017.05.066

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown