Liv.52 up-regulates cellular antioxidants and increase glucose uptake to circumvent oleic acid induced hepatic steatosis in HepG2 cells

Vidyashankar, Satyakumar; Kumar, L M Sharath; Barooah, Vandana; Varma, Rachna; Nandakumar, Krishna S.; Patki, Pralhad Sadashiv

doi:10.1016/j.phymed.2012.08.005

Cited by 16 publications

(8 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Adipocyte-derived cytokines such as adiponectin have been shown to regulate many features of NAFLD including accumulation of liver fat [18]. In addition to lipid accumulation, oleic acid-mediated HepG2 cell responses recapitulate many other aspects of NAFLD, such as oxidative stress, insulin resistance, and increased release of inflammatory cytokines [19,20]. This finding implies that oleic acid is capable of modulating the expression of a variety of genes in hepatocytes.…”

Section: Endocrine Researchmentioning

confidence: 97%

Oleic Acid-Induced Hepatic Steatosis is Coupled with Downregulation of Aquaporin 3 and Upregulation of Aquaporin 9 via Activation of p38 Signaling

Qiu

Chen

et al. 2014

Horm Metab Res

View full text Add to dashboard Cite

Excess lipid deposition in hepatocytes is a hallmark feature of nonalcoholic fatty liver disease (NAFLD). The present study was designed to explore the expression and regulation of aquaporin (AQP) 3 and AQP9 in oleic acid-induced hepatic steatosis. HepG2 cells were incubated with oleic acid at different concentrations and time points. Oil-Red-O staining and triglyceride content measurement were done to assess the extent of hepatic steatosis. The expression of AQP3 and AQP9 was assessed using quantitative real-time PCR and Western blot analyses. The mitogen-activated protein kinase (MAPK) pathways involved in the regulation of AQP3 and AQP9 expression were checked. Compared to untreated control cells, oleic acid treatment significantly (p<0.05) induced hepatic steatosis in HepG2 cells in a dose- and time-dependent fashion. Oleic acid-treated cells showed a significant reduction in the AQP3 expression and a concomitant increase in the AQP9 expression. Oleic acid exposure led to enhanced phosphorylation of p38, but not ERK1/2 or JNK MAPK. Pharmacological inhibition of p38 rather than ERK1/2 signaling significantly blocked the regulation of AQP3 and AQP9 expression by oleic acid. Oleic acid-induced hepatic steatosis in HepG2 cells is associated with the coordinated regulation of AQP3 and AQP9 via activation of p38 signaling. These findings warrant functional studies of aquaglyceroporins in NAFLD.

show abstract

Section: Endocrine Researchmentioning

confidence: 97%

Oleic Acid-Induced Hepatic Steatosis is Coupled with Downregulation of Aquaporin 3 and Upregulation of Aquaporin 9 via Activation of p38 Signaling

Qiu

Chen

et al. 2014

Horm Metab Res

View full text Add to dashboard Cite

show abstract

“…Nonetheless, its use is limited by several problems, including the scarcity of liver samples and ethical issues. HepG2 cells are therefore widely used to investigate NAFLD [6][7][8][9]. However, this cell line is derived from tumor cells, which behave differently from physiologically normal cells [10].…”

Section: Introductionmentioning

confidence: 99%

Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP‐1c in L‐02 Cells

Qin

Yin

Huang

2016

Lipids

View full text Add to dashboard Cite

Excessive fat accumulation and increased oxidative stress contribute to the pathogenesis of nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying the development of steatosis are not entirely understood. The present study was undertaken to establish an experimental model of hepatocellular steatosis with a fat overaccumulation profile in which the effects of oxidative stress could be studied in L-02 cells. We investigated the effects of free fatty acids (FFA) (palmitate:oleate, 1:2) on lipid accumulation and oxidative stress and their possible mechanisms in L-02 cells. High concentrations of fatty acids significantly induced excessive lipid accumulation and oxidative stress in L-02 cells, which could only be reversed with 50 μΜ WY14643 (the PPARα agonist). Immunoblotting and qPCR analyses revealed that FFA downregulated the expression of proliferator-activated receptor alpha (PPARα), which contributed to the increased activation of sterol regulatory element binding protein-1c (SREBP-1c). These results suggest that FFA induce lipid accumulation and oxidative stress in L-02 cells by upregulating SREBP-1c expression through the suppression of PPARα.

show abstract

Section: Resultsmentioning

confidence: 98%

“…Because it is known that glucose uptake may be influenced by factors such as feeding/fasting, exposure to low/high temperature, exercise, oxidative stress, several liver pathologies, such as steatosis and non-alcoholic fatty liver disease and liver infections, for example, by hepatitis C virus (Cunningham et al, 1985;Pencek et al, 2004;Bitar et al, 2005;Bechmann et al, 2012;Moore et al, 2012;Vidyashankar et al, 2012;Yu et al, 2013), we sought to assess the specificity of the P. berghei-induced increase in glucose uptake by infected Huh7 cells. To this end, we measured 2-NBDG uptake by Huh7 cells subjected to conditions known to induce low-temperature stress in various types of mammalian cells (Fujita, 1999), high-temperature A. Huh7 cells were infected with luciferase-expressing P. berghei sporozoites, and the culture medium was replaced 2 hpi by medium with different concentrations of glucose.…”

Section: Glucose Uptake Is Specifically Increased In Hepatic Cells Comentioning

confidence: 99%

GLUT1-mediated glucose uptake plays a crucial role duringPlasmodiumhepatic infection

Meireles

Sales-Dias

Andrade

et al. 2016

Cellular Microbiology

View full text Add to dashboard Cite

SummaryIntracellular pathogens have evolved mechanisms to ensure their survival and development inside their host cells. Here, we show that glucose is a pivotal modulator of hepatic infection by the rodent malaria parasite Plasmodium berghei and that glucose uptake via the GLUT1 transporter is specifically enhanced in P. berghei‐infected cells. We further show that ATP levels of cells containing developing parasites are decreased, which is known to enhance membrane GLUT1 activity. In addition, GLUT1 molecules are translocated to the membrane of the hepatic cell, increasing glucose uptake at later stages of infection. Chemical inhibition of GLUT1 activity leads to a decrease in glucose uptake and the consequent impairment of hepatic infection, both in vitro and in vivo. Our results reveal that changes in GLUT1 conformation and cellular localization seem to be part of an adaptive host response to maintain adequate cellular nutrition and energy levels, ensuring host cell survival and supporting P. berghei hepatic development.

show abstract

Liv.52 up-regulates cellular antioxidants and increase glucose uptake to circumvent oleic acid induced hepatic steatosis in HepG2 cells

Cited by 16 publications

References 41 publications

Oleic Acid-Induced Hepatic Steatosis is Coupled with Downregulation of Aquaporin 3 and Upregulation of Aquaporin 9 via Activation of p38 Signaling

Oleic Acid-Induced Hepatic Steatosis is Coupled with Downregulation of Aquaporin 3 and Upregulation of Aquaporin 9 via Activation of p38 Signaling

Free Fatty Acids Increase Intracellular Lipid Accumulation and Oxidative Stress by Modulating PPARα and SREBP‐1c in L‐02 Cells

GLUT1-mediated glucose uptake plays a crucial role duringPlasmodiumhepatic infection

Contact Info

Product

Resources

About