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

Inosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-<i>db</i>/<i>db</i> (<i>db</i>/<i>db</i>) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affe...

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Main Authors: Bin Zhang, Yang Xu, Jinyan Liu, Chongming Wu, Xiaohong Zhao, Lidong Zhou, Yong Xie
Format: Article
Language:English
Published: MDPI AG 2023-09-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/19/14588
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author Bin Zhang
Yang Xu
Jinyan Liu
Chongming Wu
Xiaohong Zhao
Lidong Zhou
Yong Xie
author_facet Bin Zhang
Yang Xu
Jinyan Liu
Chongming Wu
Xiaohong Zhao
Lidong Zhou
Yong Xie
author_sort Bin Zhang
collection DOAJ
description Inosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-<i>db</i>/<i>db</i> (<i>db</i>/<i>db</i>) 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.
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spelling doaj.art-4d00f3419790476393227d92efc9e1802023-11-19T14:28:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191458810.3390/ijms241914588Oral 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 LipohyperplasiaBin Zhang0Yang Xu1Jinyan Liu2Chongming Wu3Xiaohong Zhao4Lidong Zhou5Yong Xie6Institute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInstitute of Medicinal Plant Development, Chinese Academy of Medical Science & Peking Union Medical College, Malianwa North Road No. 151, Haidian District, Beijing 100193, ChinaInosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-<i>db</i>/<i>db</i> (<i>db</i>/<i>db</i>) 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.https://www.mdpi.com/1422-0067/24/19/14588inosine 5′-monophosphate (IMP)AMPKacetyl-CoAACClipohyperplasia
spellingShingle Bin Zhang
Yang Xu
Jinyan Liu
Chongming Wu
Xiaohong Zhao
Lidong Zhou
Yong Xie
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
International Journal of Molecular Sciences
inosine 5′-monophosphate (IMP)
AMPK
acetyl-CoA
ACC
lipohyperplasia
title 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_short 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
title_sort 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
topic inosine 5′-monophosphate (IMP)
AMPK
acetyl-CoA
ACC
lipohyperplasia
url https://www.mdpi.com/1422-0067/24/19/14588
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