Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease
The homeostasis of the most important nitrogen-containing intermediates, ammonia and glutamine, is a tightly regulated process in which the gut-liver axis plays a central role. Several studies revealed that nitrogen metabolism is altered in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2022-12-01
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| Series: | Frontiers in Endocrinology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2022.1058101/full |
| _version_ | 1811296307775537152 |
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| author | Teresa C. Delgado Teresa C. Delgado Javier de las Heras Javier de las Heras Javier de las Heras María L. Martínez-Chantar María L. Martínez-Chantar |
| author_facet | Teresa C. Delgado Teresa C. Delgado Javier de las Heras Javier de las Heras Javier de las Heras María L. Martínez-Chantar María L. Martínez-Chantar |
| author_sort | Teresa C. Delgado |
| collection | DOAJ |
| description | The homeostasis of the most important nitrogen-containing intermediates, ammonia and glutamine, is a tightly regulated process in which the gut-liver axis plays a central role. Several studies revealed that nitrogen metabolism is altered in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), a consensus-driven novel nomenclature for Non-Alcoholic Fatty Liver Disease (NAFLD), the most common chronic liver disease worldwide. Both increased ammonia production by gut microbiota and decreased ammonia hepatic removal due to impaired hepatic urea cycle activity or disrupted glutamine synthetase activity may contribute to hepatic ammonia accumulation underlying steatosis, which can eventually progress to hyperammonemia in more advanced stages of steatohepatitis and overt liver fibrosis. Furthermore, our group recently showed that augmented hepatic ammoniagenesis via increased glutaminase activity and overexpression of the high activity glutaminase 1 isoenzyme occurs in Fatty Liver Disease. Overall, the improved knowledge of disrupted nitrogen metabolism and metabolic miscommunication between the gut and the liver suggests that the reestablishment of altered gut-liver axis nitrogenous balance is an appealing and attractive therapeutic approach to tackle Fatty Liver Disease, a growing and unmet health problem. |
| first_indexed | 2024-04-13T05:46:28Z |
| format | Article |
| id | doaj.art-2599761a436f4211b50a0216bf47a6fd |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-04-13T05:46:28Z |
| publishDate | 2022-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-2599761a436f4211b50a0216bf47a6fd2022-12-22T02:59:56ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922022-12-011310.3389/fendo.2022.10581011058101Understanding gut-liver axis nitrogen metabolism in Fatty Liver DiseaseTeresa C. Delgado0Teresa C. Delgado1Javier de las Heras2Javier de las Heras3Javier de las Heras4María L. Martínez-Chantar5María L. Martínez-Chantar6Liver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, SpainCongenital Metabolic Disorders, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainCongenital Metabolic Disorders, Biocruces Bizkaia Health Research Institute, Barakaldo, SpainDivision of Pediatric Metabolism, Department of Pediatrics, CIBERer, Cruces University Hospital, Barakaldo, SpainDepartment of Pediatrics, University of the Basque Country (UPV/EHU), Leioa, SpainLiver Disease Lab, Center for Cooperative Research in Biosciences (CIC bioGUNE), Basque Research and Technology Alliance (BRTA), Derio, Bizkaia, SpainCentro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Carlos III National Health Institute, Madrid, SpainThe homeostasis of the most important nitrogen-containing intermediates, ammonia and glutamine, is a tightly regulated process in which the gut-liver axis plays a central role. Several studies revealed that nitrogen metabolism is altered in Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD), a consensus-driven novel nomenclature for Non-Alcoholic Fatty Liver Disease (NAFLD), the most common chronic liver disease worldwide. Both increased ammonia production by gut microbiota and decreased ammonia hepatic removal due to impaired hepatic urea cycle activity or disrupted glutamine synthetase activity may contribute to hepatic ammonia accumulation underlying steatosis, which can eventually progress to hyperammonemia in more advanced stages of steatohepatitis and overt liver fibrosis. Furthermore, our group recently showed that augmented hepatic ammoniagenesis via increased glutaminase activity and overexpression of the high activity glutaminase 1 isoenzyme occurs in Fatty Liver Disease. Overall, the improved knowledge of disrupted nitrogen metabolism and metabolic miscommunication between the gut and the liver suggests that the reestablishment of altered gut-liver axis nitrogenous balance is an appealing and attractive therapeutic approach to tackle Fatty Liver Disease, a growing and unmet health problem.https://www.frontiersin.org/articles/10.3389/fendo.2022.1058101/fullGut-liver axisnitrogen metabolismFatty Liver Diseaseammoniaglutamineglutaminase |
| spellingShingle | Teresa C. Delgado Teresa C. Delgado Javier de las Heras Javier de las Heras Javier de las Heras María L. Martínez-Chantar María L. Martínez-Chantar Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease Frontiers in Endocrinology Gut-liver axis nitrogen metabolism Fatty Liver Disease ammonia glutamine glutaminase |
| title | Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease |
| title_full | Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease |
| title_fullStr | Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease |
| title_full_unstemmed | Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease |
| title_short | Understanding gut-liver axis nitrogen metabolism in Fatty Liver Disease |
| title_sort | understanding gut liver axis nitrogen metabolism in fatty liver disease |
| topic | Gut-liver axis nitrogen metabolism Fatty Liver Disease ammonia glutamine glutaminase |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2022.1058101/full |
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