Ohmori Chinatsu, Kumamoto Eiko, Kasai Satoka, Okano Kotaro, Ota Urara, Kamiya Atsuko, Yamauchi Mitsugu, Takahashi Kiwamu, Ishizuka Masahiro, Yoshizawa Kazumi, Yamada Daisuke, Saitoh Akiyoshi
Laboratory of Pharmacology, Department of Pharmacy, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
Laboratory of Pharmacology and Therapeutics, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 6-3-1 Niijyuku, Katsushika-ku, Tokyo 125-8585, Japan.
Life (Basel). 2025 Sep 18;15(9):1465. doi: 10.3390/life15091465.
5-aminolevulinic acid (5-ALA) is a heme precursor involved in mitochondrial activation. A clinical study suggested that 5-ALA supplementation alleviates fatigue in healthy individuals who experience chronic physical tiredness. However, the detailed mechanisms are unknown. Therefore, we investigated the mechanism underlying the antifatigue effect of 5-ALA using fatigue mouse models. C57BL/6N mice were orally administered 5-ALA hydrochloride or distilled water for 8 weeks. Fatigue mouse models were developed by housing the mice in a cage filled with water for 4 days. Fatigue was evaluated through running distance via a treadmill test. The decrease in the running distance in female mice significantly recovered after 5-ALA administration. 5-ALA administration ameliorated the decreased blood glucose levels in fatigue mouse models. These results suggest that 5-ALA improves fatigue-induced hypoglycemia by promoting the use of fatty acids. PpIX's concentration in the FCX of the fatigue mouse models significantly increased after 5-ALA treatment. Decreased levels of 3-methoxy-4-hydroxyphenylglycol and noradrenaline (NA) turnover ratio in the FCX recovered to non-fatigue levels after 5-ALA treatment. Therefore, the antifatigue effect of 5-ALA in mice could be related to the activation of the NA neuronal systems in the FCX and the increase in energy production via glycogenesis activation from peripheral adipose tissue.
5-氨基酮戊酸（5-ALA）是一种参与线粒体激活的血红素前体。一项临床研究表明，补充5-ALA可缓解长期身体疲劳的健康个体的疲劳感。然而，具体机制尚不清楚。因此，我们使用疲劳小鼠模型研究了5-ALA抗疲劳作用的潜在机制。将C57BL/6N小鼠口服给予盐酸5-ALA或蒸馏水，持续8周。通过将小鼠饲养在装满水的笼子中4天来建立疲劳小鼠模型。通过跑步机测试的跑步距离来评估疲劳程度。给予5-ALA后，雌性小鼠跑步距离的减少显著恢复。给予5-ALA改善了疲劳小鼠模型中血糖水平的降低。这些结果表明，5-ALA通过促进脂肪酸的利用来改善疲劳诱导的低血糖。5-ALA处理后，疲劳小鼠模型的额叶皮质（FCX）中原卟啉IX（PpIX）的浓度显著增加。5-ALA处理后，FCX中3-甲氧基-4-羟基苯乙二醇水平的降低和去甲肾上腺素（NA）周转率恢复到非疲劳水平。因此，5-ALA对小鼠的抗疲劳作用可能与FCX中NA神经元系统的激活以及通过外周脂肪组织糖原生成激活增加能量产生有关。
