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Long term ingestion of dietary ALEs induces metabolic disorders in mice by inducing gut dysbiosis and inhibiting AMPK/SIRT1 pathway

Yaya Wanga, Tianchang Zhanga, Linqing Niea, Yan Zhanga, Junping Wangb, Shuo Wanga()
Tianjin Key Laboratory of Food Science and Health, School of Medicine, Nankai University, Tianjin 300071, China
State Key Laboratory of Food Nutrition and Safety, Key Laboratory of Food Nutrition and Safety, Ministry of Education of China, College of Food Science and Engineering, Tianjin University of Science and Technology, Tianjin 300457, China

Peer review under responsibility of Tsinghua University Press.

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Statement of Significance

• Dietary Advanced lipoxidation end products (ALEs) induce lipid accumulation in the liver of mice at an early stage, and that continuous feeding of ALEs induces inflammation, oxidative stress and hepatic insulin resistance.

• The core cause of these adverse reactions is intestinal barrier damage caused by ALEs.

• The increase in lipopolysaccharides in the liver, resulting from damage to the intestinal barrier induces hepatic lipid accumulation by modulating hepatic lipid metabolism.

• ALEs play an important role in metabolic diseases by directly or indirectly inhibiting the AMPK/SIRT1 signaling pathway.

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Abstract

Advanced lipoxidation end products (ALEs) are formed by modifying proteins with lipid oxidation products. ALEs formed in the body have been linked to diabetes and hepatic disease. However, it is not known whether ALEs formed in heat-processed foods can induce metabolic diseases. Our results indicate that dietary ALEs induce lipid accumulation in the liver of mice at an early stage and continuous feeding of ALEs induces inflammation, oxidative stress and hepatic insulin resistance. The core reason for these adverse reactions is the damage to the intestinal barrier caused by ALEs. Due to the damage to the intestinal barrier, there is an increase in lipopolysaccharides (LPS) in the liver that induces hepatic lipid accumulation by modulating hepatic lipid metabolism. Furthermore, ALEs plays a major role in the regulation of metabolic diseases by directly or indirectly inhibiting AMP activated protein kinase (AMPK)/Sirtuin 1 (SIRT1) signaling through LPS.

Keywords

Dietary advanced lipoxidation end productsMetabolic disordersAMPK/SITR1 signaling pathwayGut dysbiosisIntestinal barrier

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Food Science and Human Wellness
Volume 14 Issue 2,
February 2025
Article number: 9250029
DOI: 10.26599/FSHW.2024.9250029
Cite this article:
Wang Y, Zhang T, Nie L, et al. Long term ingestion of dietary ALEs induces metabolic disorders in mice by inducing gut dysbiosis and inhibiting AMPK/SIRT1 pathway. Food Science and Human Wellness, 2025, 14(2): 9250029. https://doi.org/10.26599/FSHW.2024.9250029
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