Sarah W. Stedman Nutrition and Metabolism Center, Duke University, Durham, NC 27704, USA.
Am J Physiol Endocrinol Metab. 2013 Feb 15;304(4):E405-13. doi: 10.1152/ajpendo.00373.2012. Epub 2012 Dec 18.
Recently, we have described a strong association of branched-chain amino acids (BCAA) and aromatic amino acids (AAA) with obesity and insulin resistance. In the current study, we have investigated the potential impact of BCAA on behavioral functions. We demonstrate that supplementation of either a high-sucrose or a high-fat diet with BCAA induces anxiety-like behavior in rats compared with control groups fed on unsupplemented diets. These behavioral changes are associated with a significant decrease in the concentration of tryptophan (Trp) in brain tissues and a consequent decrease in serotonin but no difference in indices of serotonin synaptic function. The anxiety-like behaviors and decreased levels of Trp in the brain of BCAA-fed rats were reversed by supplementation of Trp in the drinking water but not by administration of fluoxetine, a selective serotonin reuptake inhibitor, suggesting that the behavioral changes are independent of the serotonergic pathway of Trp metabolism. Instead, BCAA supplementation lowers the brain levels of another Trp-derived metabolite, kynurenic acid, and these levels are normalized by Trp supplementation. We conclude that supplementation of high-energy diets with BCAA causes neurobehavioral impairment. Since BCAA are elevated spontaneously in human obesity, our studies suggest a potential mechanism for explaining the strong association of obesity and mood disorders.
最近，我们发现支链氨基酸（BCAA）和芳香族氨基酸（AAA）与肥胖和胰岛素抵抗密切相关。在本研究中，我们研究了 BCAA 对行为功能的潜在影响。我们发现，与未补充 BCAA 的对照组相比，用 BCAA 补充高蔗糖或高脂肪饮食会导致大鼠出现类似焦虑的行为。这些行为变化与脑组织中色氨酸（Trp）浓度显著降低以及 5-羟色胺（serotonin）含量相应减少有关，但 5-羟色胺突触功能的指数没有差异。在 BCAA 喂养的大鼠中，通过在饮水中补充色氨酸可以逆转类似焦虑的行为和大脑中 Trp 水平的降低，但不能通过选择性 5-羟色胺再摄取抑制剂氟西汀来实现，这表明这些行为变化独立于色氨酸代谢的 5-羟色胺途径。相反，BCAA 补充会降低大脑中另一种色氨酸衍生代谢物犬尿氨酸的水平，而通过补充色氨酸可以使犬尿氨酸水平恢复正常。我们得出结论，用 BCAA 补充高能量饮食会导致神经行为障碍。由于人类肥胖症中 BCAA 会自发升高，我们的研究表明，这为解释肥胖症和情绪障碍之间的强相关性提供了一个潜在的机制。
