TPH2 in the dorsal Raphe nuclei regulates energy balance in a sex-dependent manner.
TPH2 in the dorsal Raphe nuclei regulates energy balance in a sex-dependent manner.
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DOI：
10.1210/endocr/bqaa183
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发表时间：
2020-10
期刊：
影响因子：
4.8
通讯作者：
Hailan Liu;Chunmei Wang;Meng Yu;Yongjie Yang;Yang He;Hesong Liu;Chen Liang;Longlong Tu;Nan Zhang;Lina Wang;Julia Wang;Feng Liu;Fang Hu;Yong Xu
中科院分区：
文献类型：
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作者：
Hailan Liu;Chunmei Wang;Meng Yu;Yongjie Yang;Yang He;Hesong Liu;Chen Liang;Longlong Tu;Nan Zhang;Lina Wang;Julia Wang;Feng Liu;Fang Hu;Yong Xu
中枢5-羟色胺（5-HT）主要由中缝背核（DRN）中的色氨酸羟化酶2（TPH2）合成，在食物摄入和体重调节中发挥着关键作用。然而，TPH2对能量平衡的生理功能尚未得到一致证实。在这里，我们系统地研究了 TPH2 对成年雄性和雌性小鼠能量稳态的影响。我们发现，对照雄性和雌性小鼠的 DRN 中含有相似数量的 TPH2 + 细胞。 DRN 中成年发病的 TPH2 缺失仅在雄性小鼠中促进食欲亢进和体重增加，但在雌性小鼠中则不然。 TPH2 的消融在男性中显着降低下丘脑阿片黑皮质素原 (POMC) 神经元活性，但在女性中仅达到适度程度。通过卵巢切除术 (OVX) 剥夺雌激素会导致雌性对照小鼠和 DRN-TPH2-KO 小鼠的食物摄入量和体重增加相当。然而，TPH2的破坏减弱了外源性E2的厌食作用，并消除了E2诱导的OVX雌性小鼠POMC神经元的激活，表明TPH2对于E2激活POMC神经元和抑制食欲是必不可少的。总之，我们的研究表明，DRN 中的 TPH2 以两性二态的方式有助于能量平衡调节。
Central 5-hydroxytryptamine (5-HT), which is primarily synthesized by tryptophan hydroxylase 2 (TPH2) in the dorsal Raphe nuclei (DRN), plays a pivotal role in the regulation of food intake and body weight. However, the physiological functions of TPH2 on energy balance have not been consistently demonstrated. Here we systematically investigated the effects of TPH2 on energy homeostasis in adult male and female mice. We found that the DRN harbors similar amount of TPH2 + cells in control male and female mice. Adult-onset TPH2 deletion in the DRN promotes hyperphagia and body weight gain only in male mice, but not in female mice. Ablation of TPH2 reduces hypothalamic pro-opiomelanocortin (POMC) neuronal activity robustly in males but only to a modest degree in females. Deprivation of estrogen by ovariectomy (OVX) causes comparable food intake and weight gain in female control and DRN-TPH2-KO mice. Nevertheless, disruption of TPH2 blunts the anorexigenic effects of exogenous E2 and abolishes E2-induced activation of POMC neurons in OVX female mice, indicating that TPH2 is indispensable for E2 to activate POMC neurons and to suppress appetite. Together, our study revealed that TPH2 in the DRN contributes to energy balance regulation in a sexually dimorphic manner.