Processes exacerbating apoptosis in non-alcoholic steatohepatitis.
Clin Sci (Lond)
; 133(22): 2245-2264, 2019 11 29.
Article
em En
| MEDLINE
| ID: mdl-31742325
ABSTRACT
Non-alcoholic fatty liver disease (NAFLD) is a significant public health concern, owing to its high prevalence, progressive nature and lack of effective medical therapies. NAFLD is a complex and multifactorial disease involving the progressive and concerted action of factors that contribute to the development of liver inflammation and eventually fibrosis. Here, we summarize fundamental molecular mechanisms underlying the pathogenesis of non-alcoholic steatohepatitis (NASH), how they are interrelated and possible translation to clinical applications. We focus on processes triggering and exacerbating apoptotic signalling in the liver of NAFLD patients and their metabolic and pathological implications. Indeed, liver injury and inflammation are cardinal histopathological features of NASH, a duo in which derailment of apoptosis is of paramount importance. In turn, the liver houses a very high number of mitochondria, crucial metabolic unifiers of both extrinsic and intrinsic signals that converge in apoptosis activation. The role of lifestyle options is also dissected, highlighting the management of modifiable risk factors, such as obesity and harmful alcohol consumption, influencing apoptosis signalling in the liver and ultimately NAFLD progression. Integrating NAFLD-associated pathologic mechanisms in the cell death context could provide clues for a more profound understating of the disease and pave the way for novel rational therapies.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Apoptose
/
Hepatopatia Gordurosa não Alcoólica
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2019
Tipo de documento:
Article