Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development
Non-alcoholic fatty liver disease (NAFLD), the most frequent cause of chronic liver disease worldwide, is associated with a plethora of metabolic comorbidities such as obesity, prediabetes, type 2 diabetes mellitus, hypertension and dyslipidemia but may be present in a significant percentage of non-...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-12-01
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| Series: | Metabolism Open |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589936821000773 |
| _version_ | 1818403898389430272 |
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| author | Junli Liu Maria Dalamaga |
| author_facet | Junli Liu Maria Dalamaga |
| author_sort | Junli Liu |
| collection | DOAJ |
| description | Non-alcoholic fatty liver disease (NAFLD), the most frequent cause of chronic liver disease worldwide, is associated with a plethora of metabolic comorbidities such as obesity, prediabetes, type 2 diabetes mellitus, hypertension and dyslipidemia but may be present in a significant percentage of non-obese subjects. Recent evidence has highlighted that NAFLD is characterized by the dysregulation of hepatokines, including fibroblast growth factor 21 (FGF21). “FGF21 resistance” observed in obesity and NAFLD is actually not fully understood. A very recent study by Hao Ying et al. in Diabetes provides new insight into the roles of hepatic stress kinase p38 and FGF21 in the pathogenesis of NAFLD. This study has shown that mechanistically, via the elevation of hepatic FGF21, p38α activation increases the influx of fatty acids from the adipose tissue to liver, resulting in hepatic ectopic lipid accumulation and insulin resistance. Despite the favorable effects of p38α activation on peripheral tissues, it may impair the hepatic FGF21 properties by enhancing the degradation of FGF21 receptor cofactor β-Klotho. Ιn the fatty liver of either mice or patients, the study has shown that p38α phosphorylation and FGF21 expression were elevated while β-Klotho protein levels were diminished. Based on the observation that mice with hepatic p38α activation exhibit not only hepatic steatosis but also reduced adiposity, which is similar to those observed in lean NAFLD, these findings may also provide a plausible explanation for the lean phenotype seen in NAFLD. In conclusion, this study highlighted previously undescribed effects of hepatic p38 activation on systemic metabolic homeostasis providing novel insights into the contribution of hepatic p38α, FGF21, and β-Klotho in the etiopathogenesis of NAFLD. |
| first_indexed | 2024-12-14T08:31:34Z |
| format | Article |
| id | doaj.art-74cdc0d1dfbe47d8aa60f441c52a73d8 |
| institution | Directory Open Access Journal |
| issn | 2589-9368 |
| language | English |
| last_indexed | 2024-12-14T08:31:34Z |
| publishDate | 2021-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Metabolism Open |
| spelling | doaj.art-74cdc0d1dfbe47d8aa60f441c52a73d82022-12-21T23:09:30ZengElsevierMetabolism Open2589-93682021-12-0112100153Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD developmentJunli Liu0Maria Dalamaga1Corresponding author. Shanghai JiaoTong University, Affiliated 6thPeople's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.; Shanghai Jiao Tong University School of Medicine, Shanghai Jiao Tong University Affiliated 6th People's Hospital, Shanghai Diabetes Institute, Shanghai, ChinaCorresponding author. Clinical Biochemistry, National and Kapodistrian University of Athens, Medical School, Greece.; Department of Biological Chemistry, Medical School, National and Kapodistrian University of Athens, 75 Mikras Asias, Goudi, 11527, Athens, GreeceNon-alcoholic fatty liver disease (NAFLD), the most frequent cause of chronic liver disease worldwide, is associated with a plethora of metabolic comorbidities such as obesity, prediabetes, type 2 diabetes mellitus, hypertension and dyslipidemia but may be present in a significant percentage of non-obese subjects. Recent evidence has highlighted that NAFLD is characterized by the dysregulation of hepatokines, including fibroblast growth factor 21 (FGF21). “FGF21 resistance” observed in obesity and NAFLD is actually not fully understood. A very recent study by Hao Ying et al. in Diabetes provides new insight into the roles of hepatic stress kinase p38 and FGF21 in the pathogenesis of NAFLD. This study has shown that mechanistically, via the elevation of hepatic FGF21, p38α activation increases the influx of fatty acids from the adipose tissue to liver, resulting in hepatic ectopic lipid accumulation and insulin resistance. Despite the favorable effects of p38α activation on peripheral tissues, it may impair the hepatic FGF21 properties by enhancing the degradation of FGF21 receptor cofactor β-Klotho. Ιn the fatty liver of either mice or patients, the study has shown that p38α phosphorylation and FGF21 expression were elevated while β-Klotho protein levels were diminished. Based on the observation that mice with hepatic p38α activation exhibit not only hepatic steatosis but also reduced adiposity, which is similar to those observed in lean NAFLD, these findings may also provide a plausible explanation for the lean phenotype seen in NAFLD. In conclusion, this study highlighted previously undescribed effects of hepatic p38 activation on systemic metabolic homeostasis providing novel insights into the contribution of hepatic p38α, FGF21, and β-Klotho in the etiopathogenesis of NAFLD.http://www.sciencedirect.com/science/article/pii/S2589936821000773Fatty liverFibroblast growth factor 21Non-alcoholic fatty liver diseasep38 mitogen-activated protein kinaseSteatosis |
| spellingShingle | Junli Liu Maria Dalamaga Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development Metabolism Open Fatty liver Fibroblast growth factor 21 Non-alcoholic fatty liver disease p38 mitogen-activated protein kinase Steatosis |
| title | Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development |
| title_full | Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development |
| title_fullStr | Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development |
| title_full_unstemmed | Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development |
| title_short | Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development |
| title_sort | emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in nafld development |
| topic | Fatty liver Fibroblast growth factor 21 Non-alcoholic fatty liver disease p38 mitogen-activated protein kinase Steatosis |
| url | http://www.sciencedirect.com/science/article/pii/S2589936821000773 |
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