Jermei Jarne, Jiao Han, Shiba Ayano, Goedhart Julia C, Tandari Roberta, Kalsbeek Andries, Struys Eduard A, Yi Chun-Xia
Department of Endocrinology and Metabolism, Amsterdam University Medical Center, Location AMC, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Amsterdam Gastroenterology, Endocrinology and Metabolism, 1105 AZ Amsterdam, The Netherlands.
Metabolites. 2025 Jun 6;15(6):375. doi: 10.3390/metabo15060375.
N-lactoyl-phenylalanine (Lac-Phe), an exercise-induced metabolite, has been shown to reduce food intake, decrease body weight and adiposity, and improve glucose homeostasis without affecting energy expenditure. Until now, Lac-Phe has mainly been investigated in blood plasma, showing its appetite-suppressing effects. Interestingly, these beneficial effects were caused by a temporary increase in Lac-Phe levels after exercise. Second, despite the central role of the central nervous system in the homeostatic control of energy metabolism, little is known about the presence and function of Lac-Phe in the brain. The goal of this study is to investigate how Lac-Phe concentrations in the brain change during the 24 h light/dark cycle. : We conducted an experiment in rats in which time-restricted running was combined with time-restricted feeding (TRF) of a high-calorie diet, after which Lac-Phe levels were measured in the hypothalamus and cortex using stable isotope dilution LC-MS/MS. Microglia were isolated from rat brains to study Lac-Phe-related gene expression. : We found that Lac-Phe levels changed over time within the 24 h light/dark cycle in the hypothalamus and/or cortex, even without exercise. Our study indicates that brain Lac-Phe is not only induced by exercise but also by high-calorie diet intake independent of exercise. Finally, we showed that microglial cells are cytosolic nonspecific dipeptidase 2 () positive and therefore able to produce Lac-Phe. Hereby, we identified in microglia as a possible key mediator of Lac-Phe production. : We conclude that high-calorie diet consumption induces Lac-Phe changes in the brain in a time-of-day manner independent of exercise. This study provides new knowledge on the presence and production of Lac-Phe in the brain. Further research is needed to elucidate the potential mechanism by which Lac-Phe reduces food intake and body weight by targeting appetite-suppressing neurons.
N-乳酰苯丙氨酸（Lac-Phe）是一种运动诱导产生的代谢产物，已被证明可减少食物摄入量、降低体重和肥胖程度，并改善葡萄糖稳态，而不影响能量消耗。到目前为止，Lac-Phe主要在血浆中进行研究，显示出其食欲抑制作用。有趣的是，这些有益作用是由运动后Lac-Phe水平的暂时升高引起的。其次，尽管中枢神经系统在能量代谢的稳态控制中起着核心作用，但关于Lac-Phe在大脑中的存在和功能却知之甚少。本研究的目的是调查大脑中Lac-Phe浓度在24小时光/暗周期内如何变化。我们在大鼠身上进行了一项实验，将限时跑步与高热量饮食的限时喂养（TRF）相结合，之后使用稳定同位素稀释液相色谱-质谱联用仪（LC-MS/MS）测量下丘脑和皮质中的Lac-Phe水平。从小鼠大脑中分离出小胶质细胞以研究与Lac-Phe相关的基因表达。我们发现，即使没有运动，下丘脑和/或皮质中的Lac-Phe水平在24小时光/暗周期内也会随时间变化。我们的研究表明，大脑中的Lac-Phe不仅由运动诱导产生，还可由独立于运动的高热量饮食摄入诱导产生。最后，我们表明小胶质细胞是胞质非特异性二肽酶2（）阳性的，因此能够产生Lac-Phe。据此，我们确定小胶质细胞中的 是Lac-Phe产生的一个可能关键介质。我们得出结论，高热量饮食的摄入以一种与运动无关的日节律方式诱导大脑中Lac-Phe的变化。本研究提供了关于大脑中Lac-Phe的存在和产生的新知识。需要进一步研究以阐明Lac-Phe通过靶向食欲抑制神经元来减少食物摄入量和体重的潜在机制。
