Publication: Intermittent fasting-induced autophagy normalization confers hepatic protection in metabolic dysfunction-associated fatty liver disease: Mechanistic insights and implications
Authors
Gehan El-Akabawy ; MoezAlIslam E. Faris ; Manoj B. Menon ; Mohamed Abdel Wahab ; Farida Hussan ; Mohd Hazim Bin Zulkaflee ; Nabil Eid ; Payal Bhatnagar
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Publisher
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Universidad de Murcia, Departamento de Biologia Celular e Histiologia
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DOI
https://doi.org/10.14670/HH-18-986
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info:eu-repo/semantics/article
Description
Abstract
Metabolic dysfunction-associated fatty liver
disease (MAFLD) is a chronic liver condition that can
progress to steatohepatitis, cirrhosis, and even liver
cancer. Macroautophagy (hereinafter referred to as
autophagy) is a pro-survival mechanism that facilitates
the lysosomal clearance of damaged organelles,
abnormal proteins, and excess lipids. A growing body of
evidence indicates that autophagy dysfunction and
reduced autophagic flux play critical roles in the
pathogenesis of MAFLD. Therefore, restoring
autophagy in MAFLD may help reduce steatosis and
prevent disease progression. Intermittent fasting (IF),
involving periods of restricted to no food intake
alternating with periods of regulated/free eating, has
been demonstrated to have beneficial effects on body
composition, glucose regulation, lipid profiles, and liver
function in studies involving both animal models of
MAFLD and human subjects. Studies involving
individuals with obesity and MAFLD have shown that
Ramadan intermittent fasting (RIF), an Islamic religious
practice that involves abstaining from food and water
intake from sunrise to sunset over approximately 30
consecutive days, significantly reduces body weight,
BMI, fat mass, and inflammatory markers while
improving liver function and steatosis. The hepatoprotective effects of RIF are associated with the
enhanced expression of autophagy-related genes and the
restoration of autophagic flux. This upregulation of
autophagy as a result of RIF makes it a potentially
promising therapeutic strategy for MAFLD. This review
summarizes various forms of IF, the mechanisms of
autophagy, and evidence of autophagy dysfunction in
MAFLD. It also explores how IF, specifically RIF, may
normalize autophagy, reduce hepatic steatosis, and
improve liver function in human subjects.
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