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.