Department of Neurobiology, Physiology and Behavior, College of Biological Sciences, University of California, Davis, CA, 95616, USA.
Biomedical Engineering Graduate Group, College of Engineering, University of California, Davis, CA, 95616, USA.
Appetite. 2024 Dec 1;203:107673. doi: 10.1016/j.appet.2024.107673. Epub 2024 Sep 12.
A growing literature suggests manipulating dietary protein status decreases sweet consumption in rodents and in humans. Underlying neurocircuit mechanisms have not yet been determined, but previous work points towards hedonic rather than homeostatic pathways. Here we hypothesized that a history of protein restriction reduces sucrose seeking by altering mesolimbic dopamine signaling in mice. We tested this hypothesis using established behavioral tests of palatability and conditioned reward, including the palatability contrast and conditioned place preference (CPP) tests. We used modern optical sensors for measuring real-time nucleus accumbens (NAc) dopamine dynamics during voluntary sucrose consumption, via fiber photometry, in male C57/Bl6J mice maintained on low-protein high-carbohydrate (LPHC) or control (CON) diet for ∼5 weeks. Our results showed that a history of protein restriction decreased the consumption of a sucrose 'dessert' in sated mice by ∼50% compared to controls [T-test, p < 0.05]. The dopamine release in NAc during sucrose consumption was reduced, also by ∼50%, in LPHC-fed mice compared to CON [T-test, p < 0.01]. Furthermore, LPHC-feeding blocked the sucrose-conditioned place preference we observed in CON-fed mice [paired T-test, p < 0.05], indicating reduced sucrose reward. This was accompanied by a 33% decrease in neuronal activation of the NAc core, as measured by c-Fos immunolabeling from brains collected directly after the CPP test [T-test, p < 0.05]. Together, these findings advance our mechanistic understanding of how dietary protein restriction decreases the consumption of sweets-by inhibiting the incentive salience of a sucrose reward, together with reduced sucrose-evoked dopamine release in NAc.
越来越多的文献表明，改变饮食中的蛋白质状态可以减少啮齿动物和人类对甜食的摄入。但其潜在的神经回路机制尚未确定，但之前的工作表明这是一种享乐而非稳态的途径。在这里，我们假设蛋白质限制的历史通过改变中脑边缘多巴胺信号来减少小鼠对蔗糖的寻求。我们使用已建立的味觉和条件性奖励行为测试，包括味觉对比和条件性位置偏好（CPP）测试来检验这一假设。我们使用现代光纤传感器，通过光纤光度法，在雄性 C57/Bl6J 小鼠中测量实时伏隔核（NAc）多巴胺动力学，这些小鼠在低蛋白高碳水化合物（LPHC）或对照（CON）饮食中维持了约 5 周。我们的结果表明，与对照组相比，蛋白质限制的历史使饱食小鼠对蔗糖“甜点”的消耗减少了约 50%[T 检验，p<0.05]。与 CON 喂养的小鼠相比，LPHC 喂养的小鼠在蔗糖消耗期间 NAc 中的多巴胺释放减少了约 50%[T 检验，p<0.01]。此外，LPHC 喂养阻断了我们在 CON 喂养的小鼠中观察到的蔗糖条件性位置偏好[配对 T 检验，p<0.05]，表明蔗糖奖励减少。这伴随着 NAc 核心神经元激活的 33%的减少，如 CPP 测试后直接从大脑中收集的 c-Fos 免疫标记物所示[T 检验，p<0.05]。总的来说，这些发现推进了我们对饮食中蛋白质限制如何通过抑制蔗糖奖励的激励价值以及伏隔核中蔗糖诱发的多巴胺释放减少来减少甜食消耗的机制理解。
