Chang Hyukki, Leem Yea-Hyun, Park Jonghoon, Park Jung-Eun, Yang Soo Jin, Kim Hee-Sun
Department of Sport and Exercise Science, Seoul Women's University, Seoul, South Korea.
Department of Molecular Medicine and Inflammation-Cancer Microenvironment Research Center, School of Medicine, Ewha Womans University, 808-1 Magok-dong, Gangseo-gu, Seoul, 07804, South Korea.
Neurochem Res. 2025 Jul 23;50(4):248. doi: 10.1007/s11064-025-04504-w.
Obesity contributes to cognitive disorders, particularly memory impairment. Physical exercise is a non-pharmacological approach for enhancing weight management and promoting brain health. Especially, high-intensity interval training (HIIT) yields results comparable to or even exceeding those of traditional aerobic exercises. However, its nootropic effects and underlying mechanisms remain unclear. This study aims to investigate the cognitive-enhancing effects of high-intensity interval training (HIIT) in the context of neurotoxicity induced by a high-calorie diet, with particular emphasis on the role of osteocalcin (OCN)/GPR158 signaling in adult hippocampal neurogenesis. Mice were fed a high-fat, high-sucrose diet (HFHSD) for 12 weeks. They then participated in an 8-week HIIT program, with the training intensity determined based on their pre-assessed maximal running capacity (MRC). HIIT efficiently regulated body weight and feeding behavior while improving MRC. It also ameliorated HFHSD-induced memory deficits, as demonstrated by the modified Y-maze test, by promoting adult hippocampal neurogenesis, which was primarily localized to the dorsal hippocampus. Moreover, HIIT markedly increased astrocytic OCN/GPR158 signaling and significantly elevated BDNF expression in astrocytes within the dentate gyrus. Activation of the AKT/GSK3β pathway was also detected in OCN-positive astrocytes. This study collectively suggests a HIIT-specific mechanism, indicating that astrocytic OCN/GPR158 may contribute significantly to memory improvement in HFHSD-fed mice through its proneurogenic effects. Therefore, HIIT could serve as an effective strategy for combating the cognitive decline associated with metabolic disorders.
肥胖会导致认知障碍，尤其是记忆损害。体育锻炼是一种增强体重管理和促进大脑健康的非药物方法。特别是，高强度间歇训练（HIIT）产生的效果与传统有氧运动相当，甚至超过传统有氧运动。然而，其益智作用及其潜在机制仍不清楚。本研究旨在探讨在高热量饮食诱导的神经毒性背景下，高强度间歇训练（HIIT）的认知增强作用，特别强调骨钙素（OCN）/GPR158信号在成年海马神经发生中的作用。小鼠喂食高脂肪、高蔗糖饮食（HFHSD）12周。然后，它们参加了一个为期8周的HIIT计划，训练强度根据预先评估的最大跑步能力（MRC）确定。HIIT有效地调节了体重和进食行为，同时提高了MRC。改良Y迷宫试验表明，HIIT还改善了HFHSD诱导的记忆缺陷，其通过促进主要定位于背侧海马的成年海马神经发生来实现。此外，HIIT显著增加了星形胶质细胞的OCN/GPR158信号，并显著提高了齿状回内星形胶质细胞中脑源性神经营养因子（BDNF）的表达。在OCN阳性星形胶质细胞中也检测到AKT/GSK3β通路的激活。本研究共同提出了一种HIIT特异性机制，表明星形胶质细胞的OCN/GPR158可能通过其促神经发生作用对HFHSD喂养小鼠的记忆改善有显著贡献。因此，HIIT可作为对抗与代谢紊乱相关的认知衰退有效策略。
