Thyroid hormone receptor beta in the ventromedial hypothalamus is essential for the physiological regulation of food intake and body weight
File(s)
Published version
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2017-06-13
Date Acceptance
2017-05-19
Citation
Cell Reports, 2017, 19 (11), pp.2202-2209
ISSN
2211-1247
Publisher
Elsevier (Cell Press)
Start Page
2202
End Page
2209
Journal / Book Title
Cell Reports
Volume
19
Issue
11
Copyright Statement
© 2017 The Author(s). This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/)
Sponsor
Biotechnology and Biological Sciences Research Council (BBSRC)
National Institute for Health Research
National Institute for Health Research
Medical Research Council (MRC)
Medical Research Council (MRC)
Medical Research Council (MRC)
Wellcome Trust
Wellcome Trust
Identifier
https://www.sciencedirect.com/science/article/pii/S2211124717307234?via%3Dihub
Grant Number
BB/F021704/1
NF-SI-0507-10337
NF-SI-0513-10080
MR/L01632X/1
MR/L01632X/1
MR/N01121X/1
101123/Z/13/A
110141/Z/15/Z
Subjects
Science & Technology
Life Sciences & Biomedicine
Cell Biology
NEUROPEPTIDE-Y
VISCERAL ADIPOSITY
ENERGY-EXPENDITURE
ARCUATE NUCLEUS
ALPHA GENE
MICE
RESISTANCE
MUTATION
NEURONS
OBESITY
VMH
appetite
body weight
energy expenditure
food intake
hypothalamus
obesity
thyroid hormone
thyroid hormone receptor beta
ventromedial hypothalamus
Animals
Body Weight
Eating
Male
Mice
Thyroid Hormone Receptors beta
Ventromedial Hypothalamic Nucleus
Ventromedial Hypothalamic Nucleus
Animals
Mice
Body Weight
Thyroid Hormone Receptors beta
Eating
Male
0601 Biochemistry and Cell Biology
1116 Medical Physiology
Publication Status
Published
Date Publish Online
2017-06-13