Journal Article Epublish 1 citation
PubMed: 38716255 DOI: 10.3389/fnins.2024.1368552
Probucol mitigates high-fat diet-induced cognitive and social impairments by regulating brain redox and insulin resistance.
Front Neurosci 18:1368552
Authors: Han-Ming Wu, Yang Vivian Yang, Na-Jun Huang, Li-Ping Fan, Ying-Ying Dai, Ke-Ting Hu, Tian-Yu Tang, Lin Liu, Yue Xu, Dong-Tai Liu, Ze-Xin Cai, Xiao-Yu Niu, Xin-Yi Ren, Zheng-Hao Yao, Hao-Yu Qin, Jian-Zhen Chen, Xi Huang, Cixiong Zhang, Xiang You, Chen Wang, Ying He, Wei Hong, Yu-Xia Sun, Yi-Hong Zhan, Shu-Yong Lin
Affiliations
- Department of Neurology, Xiang'an Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
- Department of Neurology and Department of Neuroscience, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, China.
- State Key Laboratory of Cellular Stress Biology, School of Life Sciences, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
- The Third Clinical Medical College, Fujian Medical University, Fuzhou, China.
- School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
- Laboratory Animal Center, Xiamen University, Xiamen, China.
- Institute of Metabolism and Health, Henan University, Zhengzhou, China.
- Department of Digestive Diseases, School of Medicine, Faculty of Medicine and Life Sciences, Xiamen University, Xiamen, China.
Abstract
Probucol has been utilized as a cholesterol-lowering drug with antioxidative properties. However, the impact and fundamental mechanisms of probucol in obesity-related cognitive decline are unclear. In this study, male C57BL/6J mice were allocated to a normal chow diet (NCD) group or a high-fat diet (HFD) group, followed by administration of probucol to half of the mice on the HFD regimen. Subsequently, the mice were subjected to a series of behavioral assessments, alongside the measurement of metabolic and redox parameters. Notably, probucol treatment effectively alleviates cognitive and social impairments induced by HFD in mice, while exhibiting no discernible influence on mood-related behaviors. Notably, the beneficial effects of probucol arise independently of rectifying obesity or restoring systemic glucose and lipid homeostasis, as evidenced by the lack of changes in body weight, serum cholesterol levels, blood glucose, hyperinsulinemia, systemic insulin resistance, and oxidative stress. Instead, probucol could regulate the levels of nitric oxide and superoxide-generating proteins, and it could specifically alleviate HFD-induced hippocampal insulin resistance. These findings shed light on the potential role of probucol in modulating obesity-related cognitive decline and urge reevaluation of the underlying mechanisms by which probucol exerts its beneficial effects.
MeSH
Insulin Resistance, Insulin, Social Behavior, Probucol, Brain, Cognitive Dysfunction, Diet, High-Fat, Diet, Cholesterol, Obesity