Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease
Metabolic dysfunction-associated steatotic liver disease (MASLD) and its relatively advanced form, metabolic dysfunction-associated steatohepatitis (MASH), are becoming increasingly prevalent worldwide, making their prevention and management an urgent global health priority. Central to their develop...
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| Format: | Article |
| Language: | English |
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Korean Association for the Study of the Liver
2025-07-01
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| Series: | Clinical and Molecular Hepatology |
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| Online Access: | http://e-cmh.org/upload/pdf/cmh-2025-0048.pdf |
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| author | Eiji Kakazu Masaaki Mino Tatsuya Kanto |
| author_facet | Eiji Kakazu Masaaki Mino Tatsuya Kanto |
| author_sort | Eiji Kakazu |
| collection | DOAJ |
| description | Metabolic dysfunction-associated steatotic liver disease (MASLD) and its relatively advanced form, metabolic dysfunction-associated steatohepatitis (MASH), are becoming increasingly prevalent worldwide, making their prevention and management an urgent global health priority. Central to their development are key metabolic defects, including abnormal concentrations of monosaccharides, fatty acids, and amino acids, but the complex relationships between these substances within the hepatic microenvironment remain only partially understood. Dysregulated glucose metabolism and selective insulin resistance (IR) promote hepatic gluconeogenesis, glycolysis, and de novo lipogenesis; and excessive concentrations of free fatty acids from the diet and adipose tissue drive steatosis. Emerging evidence also implies that amino acid metabolism affects mitochondrial function and redox balance. Dysfunctional mitochondrial oxidative phosphorylation and the associated increase in reactive oxygen species production further exacerbate the cellular stress, inflammation, and fibrosis. However, compared with monosaccharide and fatty acid metabolism, the role of amino acid metabolism in MASLD/MASH remains less well understood. A better understanding of the role of such metabolic dysfunction in liver pathobiology should aid the identification of more useful biomarkers and precision therapies for MASLD/MASH. |
| format | Article |
| id | doaj-art-cf59c825713a4baa8d285ba7b39708c3 |
| institution | DOAJ |
| issn | 2287-2728 2287-285X |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Korean Association for the Study of the Liver |
| record_format | Article |
| series | Clinical and Molecular Hepatology |
| spelling | doaj-art-cf59c825713a4baa8d285ba7b39708c32025-08-20T03:17:26ZengKorean Association for the Study of the LiverClinical and Molecular Hepatology2287-27282287-285X2025-07-0131377179510.3350/cmh.2025.00482237Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver diseaseEiji KakazuMasaaki Mino0Tatsuya Kanto1 Department of Liver Diseases, The Research Center for Hepatitis and Immunology, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, Japan Department of Liver Diseases, The Research Center for Hepatitis and Immunology, National Institute of Global Health and Medicine, Japan Institute for Health Security, Chiba, JapanMetabolic dysfunction-associated steatotic liver disease (MASLD) and its relatively advanced form, metabolic dysfunction-associated steatohepatitis (MASH), are becoming increasingly prevalent worldwide, making their prevention and management an urgent global health priority. Central to their development are key metabolic defects, including abnormal concentrations of monosaccharides, fatty acids, and amino acids, but the complex relationships between these substances within the hepatic microenvironment remain only partially understood. Dysregulated glucose metabolism and selective insulin resistance (IR) promote hepatic gluconeogenesis, glycolysis, and de novo lipogenesis; and excessive concentrations of free fatty acids from the diet and adipose tissue drive steatosis. Emerging evidence also implies that amino acid metabolism affects mitochondrial function and redox balance. Dysfunctional mitochondrial oxidative phosphorylation and the associated increase in reactive oxygen species production further exacerbate the cellular stress, inflammation, and fibrosis. However, compared with monosaccharide and fatty acid metabolism, the role of amino acid metabolism in MASLD/MASH remains less well understood. A better understanding of the role of such metabolic dysfunction in liver pathobiology should aid the identification of more useful biomarkers and precision therapies for MASLD/MASH.http://e-cmh.org/upload/pdf/cmh-2025-0048.pdfglucoseamino acidfatty acidlipogenesisgluconeogenesis |
| spellingShingle | Eiji Kakazu Masaaki Mino Tatsuya Kanto Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease Clinical and Molecular Hepatology glucose amino acid fatty acid lipogenesis gluconeogenesis |
| title | Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease |
| title_full | Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease |
| title_fullStr | Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease |
| title_full_unstemmed | Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease |
| title_short | Role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction-associated steatotic liver disease |
| title_sort | role of amino acids in the regulation of hepatic gluconeogenesis and lipogenesis in metabolic dysfunction associated steatotic liver disease |
| topic | glucose amino acid fatty acid lipogenesis gluconeogenesis |
| url | http://e-cmh.org/upload/pdf/cmh-2025-0048.pdf |
| work_keys_str_mv | AT eijikakazu roleofaminoacidsintheregulationofhepaticgluconeogenesisandlipogenesisinmetabolicdysfunctionassociatedsteatoticliverdisease AT masaakimino roleofaminoacidsintheregulationofhepaticgluconeogenesisandlipogenesisinmetabolicdysfunctionassociatedsteatoticliverdisease AT tatsuyakanto roleofaminoacidsintheregulationofhepaticgluconeogenesisandlipogenesisinmetabolicdysfunctionassociatedsteatoticliverdisease |