Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance.
Essential role of UCP1 modulating the central effects of thyroid hormones on energy balance.
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DOI：
10.1016/j.molmet.2016.01.008
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发表时间：
2016-04
影响因子：
8.1
通讯作者：
López M
中科院分区：
文献类型：
--
作者：
Alvarez-Crespo M;Csikasz RI;Martínez-Sánchez N;Diéguez C;Cannon B;Nedergaard J;López M
传统上，甲状腺激素（TH）的代谢效应被认为是外周介导的，即体内不同组织直接对甲状腺激素产生反应，代谢增加。另一种观点认为，代谢效应是中央调节的。我们在这里研究了在何种程度上延长，集中输注三碘甲腺原氨酸（T3）本身可以诱导全身代谢的影响和棕色脂肪组织（BAT）的产热是必不可少的这种影响的程度，通过检查解偶联蛋白1（UCP 1）基因敲除小鼠。野生型和UPC 1 KO小鼠通过使用微型泵用T3集中处理。通过间接量热法分析代谢测量，并通过RT-PCR或蛋白质印迹法分析表达。免疫组化法观察BAT的形态学和组织学变化。我们发现，中枢T3治疗导致下丘脑AMP激活蛋白激酶（AMPK）水平降低和体温升高（0.7 °C）。UCP 1是必不可少的T3诱导的能量消耗率增加，这是只观察到在热中性，特别是只有在活跃期，体重减轻增加，神经肽Y（NPY）和agouti-related肽（AgRP）的下丘脑水平的增加，并增加食物摄入量的中央T3治疗诱导。延长的中枢T3治疗还导致BAT的募集和腹股沟白色脂肪组织（iWAT）的变亮/褐变（“布朗宁”）。我们的结论是，UCP 1是必不可少的调解甲状腺激素对能量平衡的中央效应，我们认为，类似的UCP 1依赖的影响可能是其他代理商的中央能量平衡的影响。中央甲状腺激素（TH）增加棕色脂肪组织（BAT）产热。中央TH增加氧气消耗和能量消耗。中央TH增加食物摄入量。中央TH促进白色脂肪组织（WAT）的亮化/褐化。在UCP 1基因敲除小鼠中，中枢TH的所有这些代谢作用均丧失。
Classically, metabolic effects of thyroid hormones (THs) have been considered to be peripherally mediated, i.e. different tissues in the body respond directly to thyroid hormones with an increased metabolism. An alternative view is that the metabolic effects are centrally regulated. We have examined here the degree to which prolonged, centrally infused triiodothyronine (T3) could in itself induce total body metabolic effects and the degree to which brown adipose tissue (BAT) thermogenesis was essential for such effects, by examining uncoupling protein 1 (UCP1) KO mice. Wildtype and UPC1 KO mice were centrally-treated with T3 by using minipumps. Metabolic measurements were analyzed by indirect calorimetry and expression analysis by RT-PCR or western blot. BAT morphology and histology were studied by immunohistochemistry. We found that central T3-treatment led to reduced levels of hypothalamic AMP-activated protein kinase (AMPK) and elevated body temperature (0.7 °C). UCP1 was essential for the T3-induced increased rate of energy expenditure, which was only observable at thermoneutrality and notably only during the active phase, for the increased body weight loss, for the increased hypothalamic levels of neuropeptide Y (NPY) and agouti-related peptide (AgRP) and for the increased food intake induced by central T3-treatment. Prolonged central T3-treatment also led to recruitment of BAT and britening/beiging (“browning”) of inguinal white adipose tissue (iWAT). We conclude that UCP1 is essential for mediation of the central effects of thyroid hormones on energy balance, and we suggest that similar UCP1-dependent effects may underlie central energy balance effects of other agents. Central thyroid hormone (TH) increases brown adipose tissue (BAT) thermogenesis. Central TH increases oxygen consumption and energy expenditure. Central TH increases food intake. Central TH promotes britening/beiging of white adipose tissue (WAT). All these metabolic effects of central TH are lost in UCP1 knockout mice.