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Open Access

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

Huang Zhanga,b, Lan Moa, Xi Chena, Mei Lic, Maiquan Lia, Yang Xua, Maomao Zengd, Zhiyong Hed, Qingwu Shena, Jie Chend( ), Wei Quana,d( )
College of Food Science and Technology, Hunan Agricultural University, Changsha 410128, China
Henan University of Animal Husbandry and Economy, Zhengzhou 450046, China
College of Food Science and Engineering, Northwest A&F University, Yangling 712100, China
State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China

Peer review under responsibility of Tsinghua University Press.

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Abstract

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 Nε-(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.

Keywords

DiabetesCognitive dysfunctionNε-(carboxymethyl)lysineNeuroinflammationMetabolomic

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Food Science and Human Wellness
Volume 13 Issue 5,
September 2024
Pages 2970-2981
DOI: 10.26599/FSHW.2022.9250240
Cite this article:
Zhang H, Mo L, Chen X, et al. Effect of exogenous free Nε-(carboxymethyl)lysine on diabetes-associated cognitive dysfunction: neuroinflammation, and metabolic disorders. Food Science and Human Wellness, 2024, 13(5): 2970-2981. https://doi.org/10.26599/FSHW.2022.9250240

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Received: 02 February 2023
Revised: 19 May 2023
Accepted: 12 July 2023
Published: 10 October 2024
© 2024 Beijing Academy of Food Sciences. Publishing services by Tsinghua University Press.

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
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