Nutritional and Food Sciences Research Institute, Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China; MOE Key Laboratory of Coal Environmental Pathogenicity and Prevention, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.
Nutritional and Food Sciences Research Institute, Department of Nutrition and Food Hygiene, School of Public Health, Shanxi Medical University, Taiyuan, 030001, China.
Redox Biol. 2024 Nov;77:103363. doi: 10.1016/j.redox.2024.103363. Epub 2024 Sep 19.
Brain function is linked with many peripheral tissues, including the liver, where hepatic fibroblast growth factor 21 (FGF21) mediates communication between the liver and brain. Lycopene (LYC), a naturally occurring carotenoid, posses multiple health-promoting properties, including neuroprotective function. Here, we investigated the effects of LYC on age-related memory impairment and the relative contribution of liver-brain FGF21 signaling in these process. The results showed that after treatment with LYC for 3 months, brain aging and age-related cognitive deficits were effectively managed. In addition, LYC ameliorated neuronal degeneration, mitochondrial dysfunction and synaptic damage, and promoted synaptic vesicle fusion in 18-month-old mice. Notably, LYC activated liver-brain FGF21 signalling in aging mice. Whereas all these central effects of LYC were negated by blocking FGF21 via i. v. injection of adeno-associated virus in aging mice. Furthermore, recombinant FGF21 elevated mitochondrial ATP levels and enhanced synaptic vesicle fusion in mouse hippocampal HT-22 cells, which promoted neurotransmitter release. Additionally, we co-cultured hepatocytes and neurons in Transwell and found that LYC enhanced hepatocytes' support for neurons. This support included improved cell senescence, enhanced mitochondrial function, and increased axon length in co-cultured neurons. In conclusion, LYC protects against age-related cognitive deficit, partly explained by activating liver-brain FGF21 signalling, hence promoting neurotransmitters release via increasing mitochondrial ATP levels and enhancing synaptic vesicle fusion. These findings revealed that FGF21 could be a potential therapeutical target in nutritional intervention strategies to improve cognitive damage caused by aging and age-related neurodegenerative diseases.
大脑功能与许多外周组织有关，包括肝脏，肝脏成纤维细胞生长因子 21（FGF21）在肝脏和大脑之间进行通讯。番茄红素（LYC）是一种天然存在的类胡萝卜素，具有多种促进健康的特性，包括神经保护功能。在这里，我们研究了 LYC 对与年龄相关的记忆障碍的影响，以及肝脏-大脑 FGF21 信号在这些过程中的相对贡献。结果表明，经过 3 个月的 LYC 治疗，大脑衰老和与年龄相关的认知缺陷得到有效控制。此外，LYC 改善了 18 个月大的小鼠中的神经元变性、线粒体功能障碍和突触损伤，并促进了突触小泡融合。值得注意的是，LYC 激活了衰老小鼠的肝脏-大脑 FGF21 信号。然而，通过在衰老小鼠中静脉注射腺相关病毒阻断 FGF21，LYC 的所有这些中枢作用都被否定了。此外，重组 FGF21 提高了线粒体 ATP 水平，并增强了小鼠海马 HT-22 细胞中的突触小泡融合，从而促进了神经递质的释放。此外，我们将肝细胞和神经元共培养于 Transwell 中，发现 LYC 增强了肝细胞对神经元的支持。这种支持包括改善细胞衰老、增强线粒体功能和增加共培养神经元中的轴突长度。总之，LYC 可预防与年龄相关的认知缺陷，部分原因是通过激活肝脏-大脑 FGF21 信号来解释，从而通过增加线粒体 ATP 水平和增强突触小泡融合来促进神经递质的释放。这些发现表明，FGF21 可能是改善衰老和与年龄相关的神经退行性疾病引起的认知损伤的营养干预策略中的一个潜在治疗靶点。
