Effect of exogenous free N^(ε)-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction:neuroinflammation,and metabolic disorders  

作　　者：Huang Zhang Lan Mo Xi Chen Mei Li Maiquan Li Yang Xu Maomao Zeng Zhiyong He Qingwu Shen Jie Chen Wei Quan 

机构地区：[1]College of Food Science and Technology,Hunan Agricultural University,Changsha 410128,China [2]Henan University of Animal Husbandry and Economy,Zhengzhou 450046,China [3]College of Food Science and Engineering,Northwest A&F University,Yangling 712100,China [4]State Key Laboratory of Food Science and Technology,Jiangnan University,Wuxi 214122,China

出　　处：《Food Science and Human Wellness》2024年第5期2970-2981,共12页食品科学与人类健康（英文）

基　　金：supported by the National Natural Science Foundation of China(32302258,32172317);Changsha Municipal Natural Science Foundation(kq2202223).

摘　　要：Diabetes-associated cognitive dysfunction has already been attracted considerable attention.Advanced glycation end products(AGEs)from daily diets are thought to be a vital contributor to the development of this diseases.However,the effect of one of the best-characterized exogenous AGEs N^(ε)-(carboxymethyl)lysine(CML)on cognitive function is not fully reported.In the present study,diabetical Goto-Kakizaki(GK)rats were treated with free CML for 8-weeks.It was found that oral consumption of exogenous CML significantly aggravated diabetes-associated cognitive dysfunction in behavioral test.In details,exogenous CML increased levels of oxidative stress,promoted the activation of glial cells in the brain,up-regulated the release of inflammatory cytokines interleukin-6,inhibited the protein expression of the brain-derived neurotrophic factor and thus led to neuroinflammation.Furthermore,exogenous CML promoted the amyloidogenesis in the brain of GK rats,and inhibited the expression of GLUT4.Additionally,several tricarboxylic acid cycle and glutamate-glutamine/γ-aminobutyric acid cycle intermediates including pyruvate,succinic acid,glutamine,glutamate were significantly changed in brain of GK rats treated with exogenous free CML.In conclusion,exogenous free CML is a potentially noxious compounds led to aggravated diabetes-associated cognitive dysfunction which could be possibly explained by its effects on neuroinflammation,energy and neurotransmitter amino acid homeostasis.

关 键 词：Diabetes Cognitive dysfunction N^(ε)-(carboxymethyl)lysine NEUROINFLAMMATION METABOLOMIC 

分 类 号：TS201.4[轻工技术与工程—食品科学] R587.2[轻工技术与工程—食品科学与工程]