1,3-dichloro-2-propanol induced lipid accumulation by blocking autophagy flux in HepG2 cells

Lü, Jing; Fan, Yong; Liu, Meitong; Zhang, Qian; Guan, Shuang

doi:10.1016/j.tox.2021.152716

Cited by 7 publications

(7 citation statements)

References 36 publications

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“…Evidence of lipophagy has been found in models other than HFD-fed mice. It has been shown that 1,3-dichloro-2-propanol can induce lipid accumulation in HepG2 cells by reducing autophagosome formation and impairing lysosomal formation via AKT/mTOR [ 16 ]. Several studies have found that a deficiency in selective autophagy is associated with suppression of lipid oxidation.…”

Section: What Is Lipophagy?mentioning

confidence: 99%

The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders

et al. 2022

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Autophagy is a conserved method of quality control in which cytoplasmic contents are degraded via lysosomes. Lipophagy, a form of selective autophagy and a novel type of lipid metabolism, has recently received much attention. Lipophagy is defined as the autophagic degradation of intracellular lipid droplets (LDs). Although much remains unknown, lipophagy appears to play a significant role in many organisms, cell types, metabolic states, and diseases. It participates in the regulation of intracellular lipid storage, intracellular free lipid levels (e.g., fatty acids), and energy balance. However, it remains unclear how intracellular lipids regulate autophagy. Impaired lipophagy can cause cells to become sensitive to death stimuli and may be responsible for the onset of a variety of diseases, including nonalcoholic fatty liver disease and metabolic syndrome. Like autophagy, the role of lipophagy in cancer is poorly understood, although analysis of specific autophagy receptors has helped to expand the diversity of chemotherapeutic targets. These studies have stimulated increasing interest in the role of lipophagy in the pathogenesis and treatment of cancer and other human diseases.

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Section: What Is Lipophagy?mentioning

confidence: 99%

The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders

et al. 2022

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“…Previous studies have demonstrated that autophagy is involved in hepatic lipid metabolism, and autophagy blockage may result in intracellular lipid accumulation 16,30 . Thus, we speculated that Pb‐induced lipid accumulation is associated with autophagy blockage.…”

Section: Resultsmentioning

confidence: 88%

“…It is well demonstrated that autophagy is a vital process in lipid metabolism. Yang et al 17 demonstrated that bisphenol A (BPA) exposure is associated with NAFLD, induction of autophagy by Torin1 (autophagy activator) protected against BPA‐induced lipid accumulation, whereas suppression of autophagy by CQ exacerbated BPA‐induced lipid accumulation; Zhao et al 45 pointed that multi‐walled carbon nanotube (MWCNTs)‐induced lipid accumulation in HepG2 cells through the modulation of lipophagy pathway; Miyamae et al 46 suggested that tetrandrine could result in lipid accumulation in hepatic stellate cell and the blocked autophagy might be responsible for this phenomenon; Besides, our previous reports also proved that palmitic acid (PA) and 1,3‐dichloro‐2‐propanol (1,3‐DCP)‐induced lipid accumulation was related to blocked autophagy, and activation of autophagy could relieve this effect 16,30 . Currently, limited studies address the effect of Pb on lipid accumulation, and the mechanism remains unclear.…”

Section: Discussionmentioning

confidence: 99%

“…Numerous studies have demonstrated a critical function for autophagy in lipid metabolism, which is termed lipophagy. In fact, in the process of lipophagy, lipidation of microtubule associated protein light‐chain 3 (LC3) that locate in the autophagic vacuole membrane could selectively interact with lipid drops (LDs) and sequestrate LDs into double‐membrane autophagosomes, and then autophagosomes fuse with lysosomes to form autolysosomes and there is subsequent degradation of the LDs by lysosomal enzymes within the autolysosomes and finally produce free fatty acids and released into the cytoplasm 16–18 . Of importance, liver is an essential metabolic organ and highly depends on autophagy to regulate lipid metabolism and dysregulated autophagy may lead to lipid accumulation.…”

Section: Introductionmentioning

confidence: 99%

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SIRT1/mTOR pathway‐mediated autophagy dysregulation promotes Pb‐induced hepatic lipid accumulation in HepG2 cells

Mao

Zhang

Guan

et al. 2021

Environmental Toxicology

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Lead (Pb) is a common and toxic metal pollutant in the ecological environment and has drawn significant attention due to its presence in various channels, including the use of lead‐based paint, mineral extraction and smelting, exhaust gas from gasoline combustion. Autophagy is an essential catabolic pathway and blocked autophagy may result in abnormal lipid metabolism in liver. A body of evidence demonstrates that Pb exposure causes abnormal lipid droplet (LDs) accumulation in the liver, but the mechanism remains unknown. Here, we investigated whether Pb induced lipid accumulation by regulating autophagy in HepG2 cells. In this study, we found that Pb (50 μM) blocked the autophagy flux mainly by transcription factor EB (TFEB)‐mediated impairment of lysosome formation and activity. Then we demonstrated that the dense lipid accumulation was observed upon Pb exposure, and induction of autophagy by the autophagy activator rapamycin (Rap) alleviated Pb‐induced lipid accumulation, while suppression of autophagy by chloroquine (CQ) exacerbated Pb‐induced lipid accumulation, suggested that Pb‐induced autophagy blockage might be responsible for lipid accumulation. Moreover, we demonstrated that the SIRT1/mTOR pathway participated in Pb‐induced autophagy dysregulation, leading to Pb‐induced hepatic lipid accumulation. In summary, these results revealed a new insight into the relationship between Pb‐caused autophagy dysregulation and lipid accumulation for the first time and highlight autophagy as a novel therapeutic target against Pb‐induced hepatic lipid accumulation which supplying the theoretical basis and potential strategies for the intervention and treatment of Pb‐related disease.

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“…Liver cell death signals are activated during sustained or severe ERS, which has been demonstrated to associate with autophagy or apoptosis as they can be initiated by common upstream signals [11,13,14]. Autophagy normally acts as a cellular protective mechanism; nevertheless, autophagy dysfunction can lead to severe liver damage, and even cancer [15][16][17]. Hepatocyte apoptosis is considered an essential step in most forms of liver damage [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (Danio rerio)

Zhang

et al. 2021

Toxins

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It is important to note that 2-Amino-3-methylimidazole[4,5-f]quinoline (IQ) is one of the most common heterocyclic amines (HCAs), which is a class of mutagenic/carcinogenic harmful compounds mainly found in high-protein thermal processed foods and contaminated environments. However, the pre-carcinogenic toxicity of IQ to the liver and its mechanism are poorly understood, further research is needed. In light of this, we exposed zebrafish to IQ (0, 8, 80, and 800 ng/mL) for 35 days, followed by comprehensive experimental studies. Histopathological and ultrastructural analysis showed that hepatocytes were damaged. TUNEL results showed that IQ induced apoptosis of liver cells, the expression of apoptosis factor gene was significantly increased, and the expression of Bcl-2 protein was significantly decreased. In addition, upregulated expression of the 78-kDa glucose-regulated protein (GRP78) and C/EBP homologous protein (CHOP) and endoplasmic reticulum stress (ERS)-related factors transcription levels were elevated obviously, suggesting that IQ induced ERS. Decreased protein expression of autophagy-related 5 (Atg5)-Atg12, Beclin1, and LC3-II, increased protein expression of p62, and autophagy-related factors transcription levels were significantly decreased, suggesting that IQ inhibited autophagy. Overall, our research showed that the potential harm of IQ to the liver before the occurrence of liver cancer was related to ERS and its mediated autophagy and apoptosis pathways.

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1,3-dichloro-2-propanol induced lipid accumulation by blocking autophagy flux in HepG2 cells

Cited by 7 publications

References 36 publications

The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders

The regulation, function, and role of lipophagy, a form of selective autophagy, in metabolic disorders

SIRT1/mTOR pathway‐mediated autophagy dysregulation promotes Pb‐induced hepatic lipid accumulation in HepG2 cells

2-Amino-3-Methylimidazo[4,5-f]quinoline Triggering Liver Damage by Inhibiting Autophagy and Inducing Endoplasmic Reticulum Stress in Zebrafish (Danio rerio)

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