A human hepatocellular in vitro model to investigate steatosis

Gómez-Lechón, Marı́a José; Donato, M. Teresa; Martínez-Romero, Alicia; Jiménez, Núria; Castell, José V.; O’Connor, José-Enrique

doi:10.1016/j.cbi.2006.11.004

Cited by 451 publications

(406 citation statements)

References 40 publications

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“…The present study used FFAs to establish a cell model of human NAFLD. The results showed triglyceride accumulation in HepG2 cells after treatment with FFAs, consistent with previous studies [27][28][29][30].…”

Section: Discussionsupporting

confidence: 92%

“…Saturated palmitic (PA; C16:0) and monounsaturated oleic (OA; C18:1) acids are the most abundant FFAs in the liver triglycerides of patients with NAFLD [27,28]. Previous studies showed that in vitro NAFLD models induced by FFAs mixture (PA/OA, 1:2 ratio) could lead to triglyceride accumulation in hepatocytes similar to that of patients with NAFLD, with minor toxic and apoptotic effects [29,30]. The present study used FFAs to establish a cell model of human NAFLD.…”

Section: Discussionmentioning

confidence: 99%

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Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

Chen

Lin

et al. 2017

Food & Nutrition Research

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Non-alcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation unrelated to excess alcohol intake, in which the hepatic expression of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is inhibited. Long non-coding RNA HOTAIR suppresses PTEN expression in hepatic stellate cells during liver fibrosis, and it is involved in liver lipid dysregulation. In this study, we evaluated whether the PTEN down-regulation and lipid accumulation in hepatic cells might be mediated by HOTAIR during the development of NAFLD. Free fatty acids (FFAs) treatment promoted triglyceride accumulation in HepG2 cells, significantly increasing HOTAIR expression and inhibiting PTEN expression (both at mRNA and protein levels).The effects on HOTAIR and PTEN expressions disappeared after withdrawal of the FFAs treatment. SiRNAmediated HOTAIR knockdown prevented PTEN down-regulation and triglyceride accumulation in HepG2 cells treated with FFAs; and CAPE (an NF-κBp65 inhibitor) treatment prevented the HOTAIR up-regulation and PTEN down-regulation. FFAs could induce the up-regulation of HOTAIR in HepG2 cells probably dependent on the NF-κB signaling, and consequently suppress PTEN expression and promote triglyceride accumulation. Aberrant up-regulation of HOTAIR mediated by excessive circulating FFAs levels may be a crucial mechanism associated with liver steatosis. ARTICLE HISTORY

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

Chen

Lin

et al. 2017

Food & Nutrition Research

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“…Gomez-Lechona et al (28), designed a study to define an experimental model of hepatocellular steatosis, and found that a high proportion of palmitic acid (oleate/ palmitate, 0:3 ratio) might represent a cellular model of steatosis (27).…”

mentioning

confidence: 99%

High Fatty Diet Effects on Rat Liver

et al. 2014

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“…In contrast, DF-GA30 and DF-GA70 decreased caspase 3 mRNA levels, whereas DF-FW and DF-GA70 increased Bcl-2 mRNA levels in the liver. These results indicate that DF regulates apoptotic It is known that an NAFLD cell model is induced by an overload of free fatty acids (Gomez-Lechon et al, 2007;Liang et al, 2015). The previous study demonstrated that treatment of HepG2 cells with excess free fatty acids induced steatosis and regulated the mRNA expression of lipid metabolism genes (Yoon et al, 2017).…”

Section: It Is Known That Larger Adipocytes In Visceral Adiposementioning

confidence: 91%

The Herbal Composition Gangjihwan fromEphedra intermedia, Lithospermum erythrorhizonandRheum palmatumAmeliorates Hepatic Inflammation and Fibrosis in Obese C57BL/6J Mice and HepG2 Cells

Yoon

2017

BSL

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It was demonstrated that Gangjihwan (DF), which is the herbal composition composed of Ephedra intermedia, Lithospermum erythrorhizon, and Rheum palmatum, inhibits obesity and hepatic steatosis in high fat diet (HFD)-fed obese mice. The aim of this study was to determine the effects of DF on visceral obesity, hepatic inflammation and fibrosis and the mechanism of actions involved in this process using in vivo and in vitro approaches. DF was extracted with water (DF-FW), 30% grain alcohol (DF-GA30), and 70% grain alcohol (DF-GA70). Administration of DF to HFD-fed control mice decreased visceral tissue mass and visceral adipocyte size without adverse effects. Visceral fat mass was decreased by DF-GA30 and DF-GA70, and visceral adipocyte size by all three DF extracts compared with obese control mice. Histological analysis revealed that three kinds of DF extracts reduced toluidine blue-stained mast cells and collagen accumulation in the liver, the extents of which were most eminent in DF-GA70-treated mice. DF-GA70 decreased the mRNA levels of the inflammation (TNFα and VCAM-1), fibrosis (α-SMA), and apoptosis (caspase 3) genes, but increasing the anti-apoptosis gene (Bcl-2) mRNA levels in the liver of obese control mice. Consistent with the in vivo data, GA-70 also altered the expression of inflammation genes (TNFα and MCP-1) in HepG2 cells. These results indicate that DF not only inhibits visceral obesity, but also ameliorates visceral obesity-induced hepatic inflammation and fibrosis and that this process may be mediated by regulating the hepatic expression of inflammatory and fibrogenic genes.

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A human hepatocellular in vitro model to investigate steatosis

Cited by 451 publications

References 40 publications

Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

High Fatty Diet Effects on Rat Liver

The Herbal Composition Gangjihwan fromEphedra intermedia, Lithospermum erythrorhizonandRheum palmatumAmeliorates Hepatic Inflammation and Fibrosis in Obese C57BL/6J Mice and HepG2 Cells

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