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.
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DOI：
10.1016/j.celrep.2017.05.066
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发表时间：
2017-06-13
期刊：
影响因子：
8.8
通讯作者：
Gardiner JV
中科院分区：
文献类型：
--
作者：
Hameed S;Patterson M;Dhillo WS;Rahman SA;Ma Y;Holton C;Gogakos A;Yeo GSH;Lam BYH;Polex-Wolf J;Fenske W;Bell J;Anastasovska J;Samarut J;Bloom SR;Bassett JHD;Williams GR;Gardiner JV
肥胖症的流行是一个重大的全球健康问题。更好地理解调节食欲和体重的机制将为抗肥胖疗法的设计提供理论基础。甲状腺激素通过与作为配体诱导转录因子的甲状腺激素受体(TRs)相互作用，在代谢动态平衡中发挥关键作用。Tr-β亚型(trβ)在下丘脑腹内侧部表达，下丘脑腹内侧部是控制能量平衡的重要脑区。在这里，我们报告了选择性地敲除成年小鼠VMH中的TRβ，由于过度吞噬和能量消耗减少而导致严重肥胖。观察到的体重增加与最极端形式的单基因肥胖的小鼠模型的幅度相似。这些数据表明，vmh中的trβ是食物摄取和能量平衡的主要生理调节因子。小鼠下丘脑腹内侧核(Vmh)表达甲状腺激素受体β(trβ)，选择性敲除下丘脑中的trβ(trβ−)导致严重肥胖。肥胖是由于进食过多(过度吞噬)和能量消耗减少引起的，trβ−小鼠改变了下丘脑食物摄入量调节因子的表达。报道称，选择性敲除小鼠下丘脑中的一种甲状腺激素受体会导致严重肥胖、暴饮暴食和能量消耗减少的表型，这可能是由于下丘脑摄食调节因子表达的下游变化。
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. The ventromedial hypothalamus (VMH) expresses thyroid hormone receptor beta (TRβ) In mice, selective knockdown of TRβ (TRβ−) in the VMH results in severe obesity The obesity is due to overeating (hyperphagia) and reduced energy expenditure TRβ− mice have altered expression of hypothalamic regulators of food intake Hameed et al. report that selective knockdown of a thyroid hormone receptor in the mouse hypothalamus results in a phenotype of severe obesity, overeating, and reduced energy expenditure, which may be due to downstream changes in the expression of hypothalamic regulators of food intake.