Abstract：
Depression is often associated with fatigue/energy loss. However, we lack a detailed understanding of the factors explaining this association. In this study, we uncovered that depressed mice have a defect in fat absorption, resulting in weight loss and reduced circulating lipid levels. Si-Ni-San (SNS), a basic formula of traditional Chinese medicine (TCM) for the treatment of depression, was found to not only alleviate depression-like behaviors, but also reverse the weight loss and dietary fat absorption of depressed mice. We found that SNS improved body weight and circulating lipid levels of depressed mice by up-regulating proteins [such as FFA uptake protein (CD36), TAG synthesis proteins (GPAT3, MOGAT2, DGAT1 and DGAT2) and chylomicron packaging proteins (MTP and APOB)] in the fat absorption pathway. Furthermore, cell-based results conducted with LPS-stimulated mouse MODE-K and human Caco-2 cells support that SNS, as well as Sinensetin (SIN) and Nobiletin (NOB), the two active components of the formula, have a role in regulating lipid absorption. Mechanistic studies revealed that SNS reverses body weight and fat absorption defects of depressed mice in part through the NR1D1/BMAL1/DGAT2 axis. These findings advance our understanding of the crosstalk between depression and energy loss, highlight the importance of gut function in disease management, and provide a basis for the application of SNS in the clinical treatment of depression and related disorders.
摘要：
抑郁症通常与疲劳/能量损失有关。然而,我们对解释这种关联的因素缺乏详细的了解。在这项研究中,我们发现抑郁的老鼠在脂肪吸收方面有缺陷，导致体重减轻和循环脂质水平降低。Si-Ni-San(SNS)，治疗抑郁症的中医基本配方，被发现不仅能缓解抑郁样的行为，而且还可以逆转抑郁小鼠的体重减轻和饮食脂肪吸收。我们发现SNS通过上调蛋白质[如FFA摄取蛋白（CD36），改善抑郁小鼠的体重和循环脂质水平，脂肪吸收途径中的TAG合成蛋白(GPAT3、MOGAT2、DGAT1和DGAT2)和乳糜微粒包装蛋白(MTP和APOB)]。此外，用LPS刺激的小鼠MODE-K和人Caco-2细胞进行的基于细胞的结果支持SNS，以及西能塞汀（SIN）和诺比林（NOB），配方的两种活性成分，有调节脂质吸收的作用。机制研究表明，SNS部分通过NR1D1/BMAL1/DGAT2轴逆转抑郁小鼠的体重和脂肪吸收缺陷。这些发现促进了我们对抑郁和能量损失之间的串扰的理解，强调肠道功能在疾病管理中的重要性，为SNS在抑郁症及相关疾病临床治疗中的应用提供依据。
