Role of Insulin Resistance in MAFLD
Many studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying the development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). Metabo...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/8/4156 |
| _version_ | 1797537379926409216 |
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| author | Yoshitaka Sakurai Naoto Kubota Toshimasa Yamauchi Takashi Kadowaki |
| author_facet | Yoshitaka Sakurai Naoto Kubota Toshimasa Yamauchi Takashi Kadowaki |
| author_sort | Yoshitaka Sakurai |
| collection | DOAJ |
| description | Many studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying the development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). Metabolic dysfunction in this context encompasses obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, with insulin resistance as the common underlying pathophysiology. Imbalance between energy intake and expenditure results in insulin resistance in various tissues and alteration of the gut microbiota, resulting in fat accumulation in the liver. The role of genetics has also been revealed in hepatic fat accumulation and fibrosis. In the process of fat accumulation in the liver, intracellular damage as well as hepatic insulin resistance further potentiates inflammation, fibrosis, and carcinogenesis. Increased lipogenic substrate supply from other tissues, hepatic zonation of Irs1, and other factors, including ER stress, play crucial roles in increased hepatic de novo lipogenesis in MAFLD with hepatic insulin resistance. Herein, we provide an overview of the factors contributing to and the role of systemic and local insulin resistance in the development and progression of MAFLD. |
| first_indexed | 2024-03-10T12:14:21Z |
| format | Article |
| id | doaj.art-577b35060ebf483787d9e58d6fd33ca0 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T12:14:21Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-577b35060ebf483787d9e58d6fd33ca02023-11-21T15:57:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-04-01228415610.3390/ijms22084156Role of Insulin Resistance in MAFLDYoshitaka Sakurai0Naoto Kubota1Toshimasa Yamauchi2Takashi Kadowaki3Department of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanDepartment of Diabetes and Metabolic Diseases, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655, JapanToranomon Hospital, Tokyo 105-8470, JapanMany studies have reported that metabolic dysfunction is closely involved in the complex mechanism underlying the development of non-alcoholic fatty liver disease (NAFLD), which has prompted a movement to consider renaming NAFLD as metabolic dysfunction-associated fatty liver disease (MAFLD). Metabolic dysfunction in this context encompasses obesity, type 2 diabetes mellitus, hypertension, dyslipidemia, and metabolic syndrome, with insulin resistance as the common underlying pathophysiology. Imbalance between energy intake and expenditure results in insulin resistance in various tissues and alteration of the gut microbiota, resulting in fat accumulation in the liver. The role of genetics has also been revealed in hepatic fat accumulation and fibrosis. In the process of fat accumulation in the liver, intracellular damage as well as hepatic insulin resistance further potentiates inflammation, fibrosis, and carcinogenesis. Increased lipogenic substrate supply from other tissues, hepatic zonation of Irs1, and other factors, including ER stress, play crucial roles in increased hepatic de novo lipogenesis in MAFLD with hepatic insulin resistance. Herein, we provide an overview of the factors contributing to and the role of systemic and local insulin resistance in the development and progression of MAFLD.https://www.mdpi.com/1422-0067/22/8/4156NAFLDMAFLDinsulin signalinginsulin resistancede novo lipogenesis (DNL)triglycerides (TG) |
| spellingShingle | Yoshitaka Sakurai Naoto Kubota Toshimasa Yamauchi Takashi Kadowaki Role of Insulin Resistance in MAFLD International Journal of Molecular Sciences NAFLD MAFLD insulin signaling insulin resistance de novo lipogenesis (DNL) triglycerides (TG) |
| title | Role of Insulin Resistance in MAFLD |
| title_full | Role of Insulin Resistance in MAFLD |
| title_fullStr | Role of Insulin Resistance in MAFLD |
| title_full_unstemmed | Role of Insulin Resistance in MAFLD |
| title_short | Role of Insulin Resistance in MAFLD |
| title_sort | role of insulin resistance in mafld |
| topic | NAFLD MAFLD insulin signaling insulin resistance de novo lipogenesis (DNL) triglycerides (TG) |
| url | https://www.mdpi.com/1422-0067/22/8/4156 |
| work_keys_str_mv | AT yoshitakasakurai roleofinsulinresistanceinmafld AT naotokubota roleofinsulinresistanceinmafld AT toshimasayamauchi roleofinsulinresistanceinmafld AT takashikadowaki roleofinsulinresistanceinmafld |