Suryavanshi Udaykanth, Marka Nagaraju, Mallu Abhiram Charan Tej, Reddy G Bhanuprakash, Reddy V Sudhakar
Biochemistry Division, ICMR-National Institute of Nutrition, Tarnaka, Hyderabad, India.
Department of Food Science and Technology, Pondicherry University, Pondicherry, India.
Nutrition. 2025 Oct;138:112808. doi: 10.1016/j.nut.2025.112808. Epub 2025 Apr 14.
Increased consumption of a high-calorie diet results in the development of metabolic disorders and associated neurological impairments, ultimately leading to cognitive decline. Metabolic disturbances such as hyperglycaemia, systemic insulin resistance, and hyperhomocysteinemia (HHcy) are linked to neurodegenerative diseases. These conditions share a common pathogenic feature of increased susceptibility to protein misfolding and aggregation, which triggers endoplasmic reticulum (ER) stress. Vitamin B12 is vital for brain health, and its deficiency is associated with HHcy and ER stress. This study investigated the effect of vitamin B12 supplementation on diet-induced metabolic disorder-associated ER stress and neurobehavioral outcomes in mice.
Two-month-old C57BL/6J male mice were randomly assigned to three groups and fed with respective diets for 8 months: Control (C) group (B12: 25 μg/kg diet), HFHS (high-fat, high-sucrose diet; B12: 25 μg/kg), and HFHS+B12 (B12: 50 μg/kg).
Fasting blood glucose, glucose tolerance, triglycerides, and total cholesterol were similar across all groups. The HFHS diet led to body weight gain, higher insulin levels, elevated homocysteine (Hcy), and HOMA-IR compared to C group. However, B12 supplementation to HFHS mice significantly reduced Hcy levels compared to HFHS group. Additionally, the HFHS diet resulted in ER stress, neuronal apoptosis and astrogliosis in the cerebral cortex. However, B12 supplementation to HFHS group mitigated ER stress, protected against neuronal cell death, and reduced astrogliosis. Moreover, B12 supplementation enhanced neurotrophic support and reduced anxiety-like behaviour in HFHS+B12 group.
Overall, these findings suggest that B12 supplementation confers protection against Hcy-induced ER stress and apoptosis, highlighting its potential as a neuroprotective agent.
高热量饮食的摄入量增加会导致代谢紊乱及相关神经功能障碍，最终导致认知能力下降。高血糖、全身胰岛素抵抗和高同型半胱氨酸血症（HHcy）等代谢紊乱与神经退行性疾病有关。这些病症具有共同的致病特征，即对蛋白质错误折叠和聚集的易感性增加，从而引发内质网（ER）应激。维生素B12对大脑健康至关重要，其缺乏与HHcy和ER应激相关。本研究调查了补充维生素B12对饮食诱导的代谢紊乱相关ER应激及小鼠神经行为结果的影响。
将两个月大的C57BL/6J雄性小鼠随机分为三组，并分别喂食8个月：对照组（C组，维生素B12：25μg/kg饮食）、高脂高糖饮食组（HFHS组，维生素B12：25μg/kg）和HFHS + B12组（维生素B12：50μg/kg）。
所有组的空腹血糖、葡萄糖耐量、甘油三酯和总胆固醇相似。与C组相比，HFHS饮食导致体重增加、胰岛素水平升高、同型半胱氨酸（Hcy）升高和HOMA-IR升高。然而，与HFHS组相比，给HFHS小鼠补充维生素B12可显著降低Hcy水平。此外，HFHS饮食导致大脑皮质出现ER应激、神经元凋亡和星形胶质细胞增生。然而，给HFHS组补充维生素B12可减轻ER应激，防止神经元细胞死亡，并减少星形胶质细胞增生。此外，补充维生素B12增强了神经营养支持，并减少了HFHS + B12组的焦虑样行为。
总体而言，这些发现表明补充维生素B12可预防Hcy诱导的ER应激和细胞凋亡，突出了其作为神经保护剂的潜力。
