Abstract: The freshener inosine 5’-monophosphate (IMP) is a structural analogue of adenosine 5’-monophosphate (AMP), which may activate AMP-activated protein kinase (AMPK) to enhance glucose and lipid metabolism, thus alleviating the symptoms of diabetes and hyperlipidemia. However, no studies have been published to determine whether IMP and its disodium salt (IMP-Na2), a commonly used freshener in our daily life, can regulate glucose and lipid metabolism. In this study, C57/KsJ-db/db (db/db) mice at the age of six months were administered intragastrically with IMP at a dose of 50 mg/(kg mb) daily for 8 weeks. Afterwards, physiological indicators of the mice were measured. C57/BL/6j mice were allocated to a normal control group. Results showed that no significant changes in mouse body mass were observed during the administration period. Blood glucose concentration in db/db mice was lowered, but it was still remarkably higher than that in normal animals. The serum levels of triglyceride, total cholesterol, high-density lipoprotein, low-density lipoprotein, alkaline phosphatase, aspartate aminotransferase, alanine aminotr ansferase, lactate dehydrogenase were increased in the IMP administered group compared to the model group, suggesting that IMP could aggravate hyperlipidemia and liver damage in mice. Molecular interaction analysis revealed that IMP and AMPKγ subunits formed a complex that could activate AMPK to promote the oxidation and decomposition of fatty acids in vivo. In vitro experiments revealed that the lipid-lowering activity of IMP was significantly higher than that of lovastatin. It not only caused fatty acid hyperoxidation in mice to increase reactive oxygen species concentration and consequently cause liver damage, but also caused the accumulation of acetyl-CoA to aggravate lipid metabolism disorders. In conclusion, IMP may cause damage to the liver of elderly people with metabolic syndrome disorders and exacerbate lipid metabolic disorders. Accordingly, new food safety standards for IMP should be established as soon as possible.

Key words: inosine 5’-monophosphate; adenosine 5’-monophosphate-activated protein kinase; acetyl coenzyme A; lipid metabolic disorder; liver damage