Emerging role of cellular cholesterol in the pathogenesis of nonalcoholic fatty liver disease

Bashiri, Amir; Tavallaee, Ghazaleh; Li, L.; Ng, Dominic S.

doi:10.1097/mol.0b013e328361633e

Cited by 16 publications

(12 citation statements)

References 9 publications

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“…On the other hand, it is well known that oxidative stress mediates the deleterious effects of toxic bile acids and cholesterol [9, 21, 25, 32]. Our findings are in agreement with these observations, as HC fed mice exhibit increased DCFH and DHE staining following BDL compared to Chow fed mice.…”

Section: Discussionsupporting

confidence: 92%

Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

Nuño‐Lámbarri

Domínguez‐Pérez

Baulies-Domenech

et al. 2016

Oxidative Medicine and Cellular Longevity

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Nonalcoholic steatohepatitis is one of the leading causes of liver disease. Dietary factors determine the clinical presentation of steatohepatitis and can influence the progression of related diseases. Cholesterol has emerged as a critical player in the disease and hence consumption of cholesterol-enriched diets can lead to a progressive form of the disease. The aim was to investigate the impact of liver cholesterol overload on the progression of the obstructive cholestasis in mice subjected to bile duct ligation surgery. Mice were fed with a high cholesterol diet for two days and then were subjected to surgery procedure; histological, biochemical, and molecular analyses were conducted to address the effect of cholesterol in liver damage. Mice under the diet were more susceptible to damage. Results show that cholesterol fed mice exhibited increased apoptosis and oxidative stress as well as reduction in cell proliferation. Mortality following surgery was higher in HC fed mice. Liver cholesterol impairs the repair of liver during obstructive cholestasis and aggravates the disease with early fatal consequences; these effects were strongly associated with oxidative stress.

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Section: Discussionsupporting

confidence: 92%

Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

Nuño‐Lámbarri

Domínguez‐Pérez

Baulies-Domenech

et al. 2016

Oxidative Medicine and Cellular Longevity

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“…Free cholesterol accumulation in the liver is relevant to the pathogenesis of NASH (Bashiri et al , 2013; Musso et al , 2013; Arguello et al , 2015). Emerging evidence indicates a physical and metabolic connection linking LDs with the ER (Barbosa et al , 2015).…”

Section: Resultsmentioning

confidence: 99%

“…Emerging experimental and clinical data suggest that disturbed hepatic cholesterol homeostasis and free cholesterol accumulation in the liver are relevant to the pathogenesis of nonalcoholic steatohepatitis (NASH; Bashiri et al , 2013; Musso et al , 2013; Arguello et al , 2015). Critical roles for endoplasmic reticulum (ER) stress (Ashraf and Sheikh, 2015) and mitochondrial free cholesterol accumulation (Mari et al , 2006) have been suggested.…”

Section: Introductionmentioning

confidence: 99%

Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes

Makino

Hullin-Matsuda

Murate

et al. 2016

MBoC

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“…Recent data have suggested that accumulation of free cholesterol is relevant to the pathogenesis of NAFLD/NASH [31, 32]. Free cholesterol accumulation leads to liver injury through the activation of intracellular signalling pathways in Kupffer cells, stellate cells, and hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

Overexpression of apolipoprotein A-I alleviates endoplasmic reticulum stress in hepatocytes

2017

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BackgroundAbnormal lipid metabolism may contribute to an increase in endoplasmic reticulum (ER) stress, resulting in the pathogenesis of non-alcoholic steatohepatitis. Apolipoprotein A-I (apoA-I) accepts cellular free cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies have revealed that the overexpression of apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effects of apoA-I overexpression on ER stress and genes involved in lipogenesis in both HepG2 cells and mouse hepatocytes.MethodsHuman apoA-I was overexpressed in HepG2 hepatocytes, which were then treated with 2 μg/mL tunicamycin or 500 μM palmitic acid. Eight-week-old male apoA-I transgenic or C57BL/6 wild-type mice were intraperitoneally injected with 1 mg/kg body weight tunicamycin or with saline. At 48 h after injecting, blood and liver samples were collected.ResultsThe overexpression of apoA-I in the models above resulted in decreased protein levels of ER stress makers and lipogenic gene products, including sterol regulatory element binding protein 1, fatty acid synthase, and acetyl-CoA carboxylase 1. In addition, the cellular levels of triglycerides and free cholesterol also decreased. Some of gene products which are related to ER stress-associated apoptosis were also affected by apoA-I overexpression. These results suggested that apoA-I overexpression could reduce steatosis by decreasing lipid levels and by suppressing ER stress and lipogenesis in hepatocytes.ConclusionApoA-I expression could significantly reduce hepatic ER stress and lipogenesis in hepatocytes.

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Emerging role of cellular cholesterol in the pathogenesis of nonalcoholic fatty liver disease

Cited by 16 publications

References 9 publications

Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

Liver Cholesterol Overload Aggravates Obstructive Cholestasis by Inducing Oxidative Stress and Premature Death in Mice

Acute accumulation of free cholesterol induces the degradation of perilipin 2 and Rab18-dependent fusion of ER and lipid droplets in cultured human hepatocytes

Overexpression of apolipoprotein A-I alleviates endoplasmic reticulum stress in hepatocytes

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