Oral Intake of Inosine 5'-Monophosphate in Mice Promotes the Absorption of Exogenous Fatty Acids and Their Conversion into Triglycerides though Enhancing the Phosphorylation of Adenosine 5'-Monophosphate-Activated Protein Kinase in the Liver, Leading to Lipohyperplasia.

Abstract

Inosine 5'-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-db/db (db/db) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affects health after being taken by healthy animals is still unclear. Therefore, we investigated the health of C57BL/6J mice affected by IMP intake. Our data revealed that C57BL/6J mice administered 255 μM IMP daily via oral gavage for 4 months caused hyperlipidemia and an increase in body fat rate. The expressions of acetyl-CoA carboxylase 1 (ACC1) and phosphorylated acetyl-CoA carboxylase 2 (ACC2) in hepatocytes increased though the administration of IMP, promoting the phosphorylation of adenosine 5'-monophosphate-activated protein kinase (AMPK). The conversion of acetyl-CoA into triglycerides (TGs) was promoted by ACC1. These TGs were transported from the hepatocytes to avoid the development of non-alcoholic fatty liver disease (NAFLD), causing a deficiency of acetyl-CoA in the liver, and then, the increased phosphorylated ACC2 promoted the cytoplasm fatty acids entering the mitochondria and conversion into acetyl-CoA through the fatty acid β-oxidation pathway, causing a deficiency in fatty acids. Therefore, the liver showed enhanced absorption of exogenous fatty acids, which were converted into TGs, causing lipohyperplasia. In conclusion, an excessive IMP intake promotes metabolic dysfunction in adipose tissue.

• Authors: Bin Zhang, Yang Xu, Jinyan Liu, Chongming Wu, Xiaohong Zhao, Lidong Zhou, Yong Xie
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 24 Issue 19 (Sep 26 2023) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 37834038 (Publication Type: Journal Article)

Chemical References

• Protein Kinases
• Fatty Acids
• Triglycerides
• Acetyl-CoA Carboxylase
• Acetyl Coenzyme A
• Adenosine
• Inosine
• AMP-Activated Protein Kinases

Topics

• Mice
• Animals
• Protein Kinases (metabolism)
• Fatty Acids (metabolism)
• Triglycerides (metabolism)
• Phosphorylation
• Acetyl-CoA Carboxylase (metabolism)
• Acetyl Coenzyme A (metabolism)
• Mice, Inbred C57BL
• Liver (metabolism)
• Obesity (metabolism)
• Adenosine (metabolism)
• Inosine (metabolism)
• AMP-Activated Protein Kinases (metabolism)