Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.
Vitamin D3: A Role in Dopamine Circuit Regulation, Diet-Induced Obesity, and Drug Consumption.
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DOI：
10.1523/eneuro.0122-15.2016
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发表时间：
2016-03
期刊：
影响因子：
3.4
通讯作者：
DiLeone RJ
中科院分区：
文献类型：
--
作者：
Trinko JR;Land BB;Solecki WB;Wickham RJ;Tellez LA;Maldonado-Aviles J;de Araujo IE;Addy NA;DiLeone RJ
微量营养素对多巴胺系统的影响还没有明确的定义。在小鼠身上，我们展示了减少饮食中维生素D3(胆钙化醇)在高脂肪饮食时促进饮食诱导肥胖(DIO)、食物摄入量和药物消耗方面的潜在作用。为了补充这些缺乏症研究，用外源完全活性维生素D3(骨化三醇，10微克/公斤，i.p.)治疗。都进行了手术。用高脂饮食使瘦素抵抗的非缺陷小鼠在外源性骨化三醇急性治疗后显示出食物摄入量和体重减少。中脑的多巴胺神经元及其纹状体的靶神经元表达维生素D3受体蛋白。急性骨化三醇治疗导致幼龄小鼠这些区域多巴胺相关基因转录的变化，促进苯丙胺诱导的幼龄小鼠和大鼠的多巴胺释放，并增加急性苯丙胺治疗(2.5 mg/kg，ip)后的运动活动。或者，与各自的对照组相比，长期喂食减少的D3高脂饮食或饮食的小鼠在急性苯丙胺治疗后表现出较少的活动。最后，被训练口服液体苯丙胺(90毫克/L)的高脂肪缺乏小鼠表现出更多的摄入量，而用骨化三醇治疗的非缺乏的小鼠表现出更少的摄入量。我们的发现表明，饮食D3的减少可能是环境因素增加DIO以及高脂肪饮食时药物摄入量的原因之一。此外，这些数据表明，多巴胺回路受到D3信号的调制，并可能成为外源性骨化三醇的直接或间接靶点。
The influence of micronutrients on dopamine systems is not well defined. Using mice, we show a potential role for reduced dietary vitamin D3 (cholecalciferol) in promoting diet-induced obesity (DIO), food intake, and drug consumption while on a high fat diet. To complement these deficiency studies, treatments with exogenous fully active vitamin D3 (calcitriol, 10 µg/kg, i.p.) were performed. Nondeficient mice that were made leptin resistant with a high fat diet displayed reduced food intake and body weight after an acute treatment with exogenous calcitriol. Dopamine neurons in the midbrain and their target neurons in the striatum were found to express vitamin D3 receptor protein. Acute calcitriol treatment led to transcriptional changes of dopamine-related genes in these regions in naive mice, enhanced amphetamine-induced dopamine release in both naive mice and rats, and increased locomotor activity after acute amphetamine treatment (2.5 mg/kg, i.p.). Alternatively, mice that were chronically fed either the reduced D3 high fat or chow diets displayed less activity after acute amphetamine treatment compared with their respective controls. Finally, high fat deficient mice that were trained to orally consume liquid amphetamine (90 mg/L) displayed increased consumption, while nondeficient mice treated with calcitriol showed reduced consumption. Our findings suggest that reduced dietary D3 may be a contributing environmental factor enhancing DIO as well as drug intake while eating a high fat diet. Moreover, these data demonstrate that dopamine circuits are modulated by D3 signaling, and may serve as direct or indirect targets for exogenous calcitriol.