Lipid accumulation impairs lysosomal acid lipase activity in hepatocytes: Evidence in NAFLD patients and cell cultures

Gomaraschi, Monica; Dongiovanni, Paola; Pavanello, Chiara; Giorgio, Eleonora; Dalt, L. Da; Norata, Giuseppe Danilo; Calabresi, Laura; Consonni, Dario; Lombardi, Rosa; Branchi, Adriana

doi:10.1016/j.bbalip.2019.158523

Cited by 23 publications

(17 citation statements)

References 34 publications

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“…Therefore, efforts must be made to reduce the burden of NAFLD.NAFLD is characterized by abnormal lipid accumulation in hepatocytes (Boutari et al, 2018). Studies have revealed that being overweight, oxidative stress, and insulin resistance are the main causes of NAFLD (Gomaraschi et al, 2019;Rives et al, 2020). NAFLD can progressively develop into cirrhosis and subsequently into hepatocellular carcinoma.…”

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confidence: 99%

Protective effects of Dendrobium candidum Wall ex Lindl. on high‐fat diet‐induced liver damage in mice

Yin

Chi

Zhang³

et al. 2021

J. Food Biochem.

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Lifestyle changes in modern society has led to higher consumption of high-fat and high-cholesterol foods. The incidence of nonalcoholic fatty liver disease (NAFLD) is increasing, and the age of onset is reducing. Approximately 25%-45% of adults worldwide are affected by NAFLD (Bellentani et al., 2010); NAFLD has become the first liver disease to occur in developed countries. In China, it is the secondmost common liver disease after viral hepatitis and its incidence has been increasing continuously (Zhou et al., 2019). Therefore, efforts must be made to reduce the burden of NAFLD.NAFLD is characterized by abnormal lipid accumulation in hepatocytes (Boutari et al., 2018). Studies have revealed that being overweight, oxidative stress, and insulin resistance are the main causes of NAFLD (Gomaraschi et al., 2019;Rives et al., 2020). NAFLD can progressively develop into cirrhosis and subsequently into hepatocellular carcinoma. The incidence of cirrhosis in patients with NAFLD occurring within 10 years of onset is as high as 25% (Bhagat

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mentioning

confidence: 99%

Protective effects of Dendrobium candidum Wall ex Lindl. on high‐fat diet‐induced liver damage in mice

Yin

Chi

Zhang³

et al. 2021

J. Food Biochem.

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“…LAL is responsible for the hydrolysis of cholesteryl esters, TG, and LDL particles into free cholesterol and fatty acids. Thus, its functional impairment induces the accumulation of these un-hydrolyzed compounds in hepatocytes, whereby favoring hypercholesterolemia, cardiovascular disease, hepatic steatosis and cirrhosis [161,162].…”

Section: Genetic Landscape In Mafld Pathophysiologymentioning

confidence: 99%

Genetic and metabolic factors: the perfect combination to treat metabolic associated fatty liver disease

Meroni

Longo

Dongiovanni

2020

Exploration of Medicine

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The prevalence of nonalcoholic or more recently re-defined metabolic associated fatty liver disease (MAFLD) is rapidly growing worldwide. It is characterized by hepatic fat accumulation exceeding 5% of liver weight not attributable to alcohol consumption. MAFLD refers to an umbrella of conditions ranging from simple steatosis to nonalcoholic steatohepatitis which may finally progress to cirrhosis and hepatocellular carcinoma. MAFLD is closely related to components of the metabolic syndrome and to environmental factors. In addition to the latter, genetic predisposition plays a key role in MAFLD pathogenesis and strictly contributes to its progressive forms. The candidate genes which have been related to MAFLD hereditability are mainly involved in lipids remodeling, lipid droplets assembly, lipoprotein packaging and secretion, de novo lipogenesis, and mitochondrial redox status. In the recent years, it has emerged the opportunity to translate the genetics into clinics by aggregating the genetic variants mostly associated with MAFLD in polygenic risk scores. These scores might be used in combination with metabolic factors to identify those patients at higher risk to develop more severe liver disease and to schedule an individual therapeutic approach.

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“…The widely accepted 'multiple hits' hypothesis suggests that excessive oxidative metabolites and lipid peroxidation occur as a result of insulin resistance (ir). This causes oxidative stress (oS) and continuously damages the mitochondria within hepatocytes, while producing inflammatory mediators and cytokines (1,3). Hepatocytic inflammation and necrosis with steatosis is referred to as non-alcoholic steatohepatitis (naSH).…”

Section: Introductionmentioning

confidence: 99%

“…Hepatocytic inflammation and necrosis with steatosis is referred to as non-alcoholic steatohepatitis (naSH). Without intervention, NASH can exacerbate IR and inflammation, causing fatty liver accumulation and increasing the risk of liver cirrhosis and cancer (1,3). currently, effective naFld treatment is still lacking (4).…”

Section: Introductionmentioning

confidence: 99%

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Expression of Notch family is altered in non‑alcoholic fatty liver disease

Ding

Chen

et al. 2020

Mol Med Rep

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The aim of the present study was to explore the dynamic relationship between notch and non-alcoholic fatty liver disease (naFld), both in vitro and in vivo. The lX2, Huh7 and MiHa hepatic cell lines were used to establish a cell steatosis model induced by palmitic acid (Pa) at different concentrations (0.1, 0.25 and 0.5 mM). cell proliferation and migration were assessed using a 5-bromo-2'-deoxyuridine kit and a wound healing assay. The dosage of 0.25 mM Pa for 36-48 h treatment was chosen for subsequent experiments. Steatotic cells were identified by Oil Red O staining. Feeding mice a methionine-choline-deficient (MCD) diet is known induce a model of naFld, compared with a methionine-choline-sufficient (MCS) diet. Therefore, Notch family mrna expression was evaluated in the liver of Mcd-fed mice at varying time points (days 5, 10, 21 and 70) using reverse transcription-quantitative Pcr. notch expression levels were also assessed in cell lines at 12, 24, 36 and 48 h after Pa treatment. notch signaling molecules changed in the Pa or Mcd model over time. In vitro, the mrna levels of notch1,-2 and-4 increased in all cell lines after 12-h Pa treatment. at 24 h, these genes were upregulated only in lX2 cells, while showing a 'down-up' pattern in MiHa cells (i.e. these genes were downregulated at 24 h but upregulated at 36 h). However, expression of Notch1,-2,-3 and-4 mRNA rose significantly in the early stage (day 10) of naFld. at week 3, the levels of notch1 and-2 were higher in the Mcd group than in the McS group, while the reverse was observed for notch3 and-4. expression of these four genes increased again in the late stage (day 70) of naFld. Therefore, these results indicated that notch family members notch1-4 were involved in the development of naFld and played an important role in steatosis in this model.

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Lipid accumulation impairs lysosomal acid lipase activity in hepatocytes: Evidence in NAFLD patients and cell cultures

Cited by 23 publications

References 34 publications

Protective effects of Dendrobium candidum Wall ex Lindl. on high‐fat diet‐induced liver damage in mice

Protective effects of Dendrobium candidum Wall ex Lindl. on high‐fat diet‐induced liver damage in mice

Genetic and metabolic factors: the perfect combination to treat metabolic associated fatty liver disease

Expression of Notch family is altered in non‑alcoholic fatty liver disease

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