Abstract
Nonalcoholic fatty liver disease (NAFLD) is globally prevalent and characterized by abnormal lipid accumulation in the liver, frequently accompanied by insulin resistance (IR), enhanced hepatic inflammation, and apoptosis. Recent studies showed that endoplasmic reticulum stress (ERS) at the subcellular level underlies these featured pathologies in the development of NAFLD. As an effective treatment, exercise significantly reduces hepatic lipid accumulation and thus alleviates NAFLD. Confusingly, these benefits of exercise are associated with increased or decreased ERS in the liver. Further, the interaction between diet, medication, exercise types, and intensity in ERS regulation is more confusing, though most studies have confirmed the benefits of exercise. In this review, we focus on understanding the role of exercise-modulated ERS in NAFLD and ERS-linked molecular pathways. Moderate ERS is an essential signaling for hepatic lipid homeostasis. Higher ERS may lead to increased inflammation and apoptosis in the liver, while lower ERS may lead to the accumulation of misfolded proteins. Therefore, exercise acts like an igniter or extinguisher to keep ERS at an appropriate level by turning it up or down, which depends on diet, medications, exercise intensity, etc. Exercise not only enhances hepatic tolerance to ERS but also prevents the malignant development of steatosis due to excessive ERS.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is characterized by abnormal fat metabolism in the liver due to nonalcoholic causes [1]
The unfolded protein response (UPR) is regulated by three transmembrane proteins: protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring protein 1α (IRE-1α), and activating transcription factor 6 (ATF6)
Most studies support the benefits of exercise for NAFLD
Summary
Nonalcoholic fatty liver disease (NAFLD) is characterized by abnormal fat metabolism in the liver due to nonalcoholic causes [1]. Obesity-related insulin resistance (IR) and ectopic lipid accumulation cause hepatic steatosis [1], followed by increased lipid toxicity, leading to malignant development of liver inflammation and hepatocyte apoptosis [3]. The first hit is the excessive accumulation of fat in hepatocytes, leading to IR. Endoplasmic reticulum stress (ERS) has been proposed to understand the pathology of NAFLD [5], in which ERS causes hepatic IR, lipid accumulation, inflammation, and hepatocyte apoptosis. Exercise may modulate ERS levels in multiple organs, leading to improved lipid homeostasis in the liver and even the whole body [9, 10]. What role does ERS play in hepatic lipid accumulation? In this review, we will focus on understanding the role of up- or downregulation of ERS during exercise in NAFLD
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have