scholarly journals Gallic Acid Inhibits Lipid Accumulation via AMPK Pathway and Suppresses Apoptosis and Macrophage-Mediated Inflammation in Hepatocytes

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1479
Author(s):  
Miori Tanaka ◽  
Akari Sato ◽  
Yoshimi Kishimoto ◽  
Hideaki Mabashi-Asazuma ◽  
Kazuo Kondo ◽  
...  
Keyword(s):  
Liver Disease ◽  
Gallic Acid ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Molecular Mechanisms ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Apoptosis And Inflammation ◽  
Amp Activated Protein Kinase

Nonalcoholic fatty liver disease (NAFLD) is one of the most common causes of chronic liver disease, sometimes ranges from simple steatosis to nonalcoholic steatohepatitis (NASH). Various hits including excessive hepatic steatosis, oxidative stress, apoptosis, and inflammation, contribute to NASH development. Gallic acid (GA), a natural polyphenol, was reported to exert a protective effect on hepatic steatosis in animal models, but the precise molecular mechanisms remain unclear. Here, we examined the effect of GA on hepatic lipid accumulation, apoptosis, and inflammatory response caused by hepatocyte–macrophage crosstalk. We demonstrated that GA attenuated palmitic acid (PA)-induced fat accumulation via the activation of AMP-activated protein kinase (AMPK) in HepG2 cells. GA also ameliorated cell viability and suppressed apoptosis-related gene expression and caspase 3/7 activity induced by PA and H2O2. In a co-culture of lipid-laden Hepa 1-6 hepatocytes and RAW 264 macrophages, GA reduced inflammatory mediator expression and induced antioxidant enzyme expression. These results indicate that GA suppresses hepatic lipid accumulation, apoptosis, and inflammation caused by the interaction between hepatocytes and macrophages. The potential effects of GA observed in our study could be effective in preventing NASH and its complications.

scholarly journals Understanding the Role of Exercise in Nonalcoholic Fatty Liver Disease: ERS-Linked Molecular Pathways

2020 ◽  
Vol 2020 ◽  
pp. 1-15
Author(s):  
Yong Zou ◽  
Zhengtang Qi
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Molecular Pathways ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

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.

Simultaneous co-assembly of fenofibrate and ketoprofen peptide for the dual-targeted treatment of nonalcoholic fatty liver disease (NAFLD)

2020 ◽  
Vol 56 (36) ◽  
pp. 4922-4925 ◽  
Author(s):  
Zhongyan Wang ◽  
Chuanrui Ma ◽  
Yuna Shang ◽  
Lijun Yang ◽  
Jing Zhang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Inflammatory Responses ◽  
Targeted Treatment ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

An ingenious co-assembled nanosystem based on fenofibrate and ketoprofen peptide for the dual-targeted treatment of NAFLD by reducing hepatic lipid accumulation and inflammatory responses.

scholarly journals Macrovesicular steatosis in nonalcoholic fatty liver disease is a consequence of purine nucleotide cycle driven fumarate accumulation

2020 ◽  
Author(s):  
Matthew C. Sinton ◽  
Baltasar Lucendo Villarin ◽  
Jose Meseguer Ripolles ◽  
Sara Wernig-Zorc ◽  
John P. Thomson ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Purine Nucleotide ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Purine Nucleotide Cycle

SummaryNonalcoholic fatty liver disease (NAFLD) affects ~88% of obese individuals and is characterised by hepatic lipid accumulation. Mitochondrial metabolic dysfunction is a feature of NAFLD. We used a human pluripotent stem cell-based system to determine how mitochondrial dysfunction is linked to hepatic lipid accumulation. We induced lipid accumulation in hepatocyte-like cells (HLCs) using lactate, pyruvate and octanoate (LPO). Transcriptomic analysis revealed perturbation of mitochondrial respiratory pathways in LPO exposed cells. Using 13C isotopic tracing, we identified truncation of the TCA cycle in steatotic HLCs. We show that increased purine nucleotide cycle (PNC) activity fuels fumarate accumulation and drives lipid accumulation in steatotic cells. These findings provide new insights into the pathogenesis of hepatic steatosis and may lead to an improved understanding of the metabolic and transcriptional rewiring associated with NAFLD.

scholarly journals Sulforaphane Attenuates Nonalcoholic Fatty Liver Disease by Inhibiting Hepatic Steatosis and Apoptosis

Nutrients ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 76
Author(s):  
Jinwang Li ◽  
Siyu Xie ◽  
Wendi Teng
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Molecular Mechanisms ◽  
Lipid Deposition ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) is characterized by lipotoxicity and ectopic lipid deposition within hepatocytes. Sulforaphane (SFA), an active compound used for inhibiting tumors, was found to have the potency to improve lipid metabolism. However, its molecular mechanisms on ameliorating NAFLD are still incompletely understood. This research evaluated if SFA could inhibit hepatic steatosis and apoptosis. The effects of SFA on cell viability, lipid accumulation, triglyceride (TG) contents, apoptosis, ceramide contents, and reactive oxygen species (ROS) levels were analyzed in palmitic acid (PA)-treated HepG2 cells and high-fat diet (HFD)-fed mice. The related molecular mechanisms were further explored in hepatocytes. The results showed SFA alleviated lipid accumulation and regulated AMPK/SREBP1c/FAS signaling pathway in PA-stressed HepG2 cells. In addition, SFA alleviated PA-mediated apoptosis, downregulated the expressions of cleaved caspase 3, as well as reduced ceramide contents and ROS levels. Moreover, SFA treatment reduced HFD-induced body weight gain, alleviated insulin resistance, decreased serum TG, total cholesterol (TC), and alanine aminotransferase (ALT) levels, and prevented lipid deposition and apoptosis in the liver. This study showed SFA suppressed lipid deposition and apoptosis both in vitro and in vivo, indicating that SFA may be a potential candidate for preventing and treating NAFLD.

Ellagic acid ameliorates AKT-driven hepatic steatosis in mice by suppressing de novo lipogenesis via the AKT/SREBP-1/FASN pathway

2019 ◽  
Vol 10 (6) ◽  
pp. 3410-3420 ◽  
Author(s):  
Cong Zhang ◽  
Junjie Hu ◽  
Lei Sheng ◽  
Ming Yuan ◽  
Yong Wu ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Ellagic Acid ◽  
Lipid Accumulation ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Ellagic acid alleviates hepatic lipid accumulation in mice by suppressing AKT-driven de novo lipogenesis.

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