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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Autores principales:	Junli Liu, Maria Dalamaga
Formato:	article
Lenguaje:	EN
Publicado:	Elsevier 2021
Materias:	Fatty liver Fibroblast growth factor 21 Non-alcoholic fatty liver disease p38 mitogen-activated protein kinase Steatosis Physiology QP1-981 Biochemistry QD415-436
Acceso en línea:	https://doaj.org/article/74cdc0d1dfbe47d8aa60f441c52a73d8
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spelling	oai:doaj.org-article:74cdc0d1dfbe47d8aa60f441c52a73d82021-12-04T04:35:38ZEmerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development2589-936810.1016/j.metop.2021.100153https://doaj.org/article/74cdc0d1dfbe47d8aa60f441c52a73d82021-12-01T00:00:00Zhttp://www.sciencedirect.com/science/article/pii/S2589936821000773https://doaj.org/toc/2589-9368Non-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.Junli LiuMaria DalamagaElsevierarticleFatty liverFibroblast growth factor 21Non-alcoholic fatty liver diseasep38 mitogen-activated protein kinaseSteatosisPhysiologyQP1-981BiochemistryQD415-436ENMetabolism Open, Vol 12, Iss , Pp 100153- (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Fatty liver Fibroblast growth factor 21 Non-alcoholic fatty liver disease p38 mitogen-activated protein kinase Steatosis Physiology QP1-981 Biochemistry QD415-436
spellingShingle	Fatty liver Fibroblast growth factor 21 Non-alcoholic fatty liver disease p38 mitogen-activated protein kinase Steatosis Physiology QP1-981 Biochemistry QD415-436 Junli Liu Maria Dalamaga Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development
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.
format	article
author	Junli Liu Maria Dalamaga
author_facet	Junli Liu Maria Dalamaga
author_sort	Junli Liu
title	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_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_sort	emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in nafld development
publisher	Elsevier
publishDate	2021
url	https://doaj.org/article/74cdc0d1dfbe47d8aa60f441c52a73d8
work_keys_str_mv	AT junliliu emergingrolesforstresskinasep38andstresshormonefibroblastgrowthfactor21innaflddevelopment AT mariadalamaga emergingrolesforstresskinasep38andstresshormonefibroblastgrowthfactor21innaflddevelopment
_version_	1718372918700802048

Emerging roles for stress kinase p38 and stress hormone fibroblast growth factor 21 in NAFLD development

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