scholarly journals Resveratrol Limits Lipogenesis and Enhance Mitochondrial Activity in HepG2 Cells

2018 ◽  
Vol 21 ◽  
pp. 504-515 ◽  
Author(s):  
Magdalena Izdebska ◽  
Mariola Herbet ◽  
Monika Gawrońska-Grzywacz ◽  
Iwona Piątkowska-Chmiel ◽  
Agnieszka Korga ◽  
...  
Keyword(s):  
High Glucose ◽  
Hepg2 Cells ◽  
De Novo ◽  
Nile Red ◽  
Developed Countries ◽  
De Novo Lipogenesis ◽  
Mitochondrial Activity ◽  
Nonalcoholic Fatty Liver ◽  
Natural Polyphenol ◽  
Red Dye

Purpose: The aim of this study was to evaluate the effect of resveratrol on de novo lipogenesis in HepG2 cells caused by high glucose concentrations. Increased lipogenesis in the liver is the main reason for the development of nonalcoholic fatty liver disease (NAFLD) - currently one of the most common chronic liver diseases. In developed countries, this disease is mostly associated with nutritional disorders, resulting from the increasing consumption of monosaccharides. Resveratrol is a natural polyphenol with a promising potential for NAFLD treatment. Methods: The steatosis of HepG2 cells was visualized using the intracellular lipid staining by Nile Red dye with a fluorescence microscope. This study also evaluated the effect of resveratrol on the mitochondrial activity (MitoTracker Green staining), dsDNA (Hoechst 33342 staining) and the viability of HepG2 cells treated with high glucose concentrations (25 and 33 mM). Results: Current study showed that high glucose concentrations induced fat-overloading in HepG2 cells (microvacuolar steatosis occurred in most of the cells). Resveratrol (20 μM) limits the steatosis induction in HepG2 cells by glucose and increased the mitochondrial activity of cells. Resveratrol did not affect the viability of HepG2 cells. Conclusion: This beneficial effect could be helpful in the treatment of NAFLD.

The beneficial effects of resveratrol on steatosis and mitochondrial oxidative stress in HepG2 cells

2017 ◽  
Vol 95 (12) ◽  
pp. 1442-1453 ◽  
Author(s):  
Magdalena Izdebska ◽  
Iwona Piątkowska-Chmiel ◽  
Agnieszka Korolczuk ◽  
Mariola Herbet ◽  
Monika Gawrońska-Grzywacz ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Fatty Acids ◽  
Palmitic Acid ◽  
Hepg2 Cells ◽  
Nile Red ◽  
Developed Countries ◽  
Mitochondrial Oxidative Stress ◽  
Nonalcoholic Fatty Liver ◽  
Beneficial Effects ◽  
Red Dye

Nonalcoholic fatty liver disease (NAFLD) is currently one of the most common chronic liver diseases, especially in developed countries. One group of substances with a potential use in the treatment of NAFLD are plant polyphenols, represented by resveratrol. The aim of this study was to evaluate the effect of resveratrol on steatosis and oxidative stress in HepG2 cells. The steatosis of cells was carried out using free fatty acids: oleic or palmitic acid and their mixtures. Steatosis was visualized using the intracellular lipid staining by Nile Red dye with a fluorescence microscope. This study also determined the viability of cells and mitochondrial membrane potential. The current study showed that fatty acids and their mixtures induced fat overloading in HepG2 cells. In the group of cells incubated with oleic acid (OA), observed changes were moderate with prevailing micro-vesicular steatosis. In case of cells incubated with palmitic acid (PA) and the mixtures of fatty acids, micro- and macro-vacuolar steatosis occurred in most of the cells. Resveratrol decreased steatosis in HepG2 cells induced by OA, PA, as well as their mixtures, and in most of experimental groups did not reduce cells viability. Resveratrol reduced the oxidative stress in HepG2 cells treated with fatty acids mixtures.

scholarly journals Concepts and Treatment Approaches in Nonalcoholic Fatty Liver Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Dina L. Halegoua-De Marzio ◽  
Jonathan M. Fenkel
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
De Novo ◽  
Imaging Techniques ◽  
De Novo Lipogenesis ◽  
Central Adiposity ◽  
Preventative Care ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD) affects up to 30% of adults and is the most common liver disease in Western nations. NAFLD is associated with central adiposity, insulin resistance, type 2 diabetes mellitus, hyperlipidemia, and cardiovascular disease. It encompasses the entire spectrum of fatty liver diseases from simple steatosis to nonalcoholic steatohepatitis (NASH) with lobular/portal inflammation, hepatocellular necrosis, and fibrosis. Of those who develop NASH, 15–25% will progress to end stage liver disease and hepatocellular carcinoma over 10–20 years. Its pathogenesis is complex, and involves a state of lipid accumulation due to increased uptake of free fatty acids into the liver, impaired fatty acid beta oxidation, and increased incidence of de novo lipogenesis. Plasma aminotransferases and liver ultrasound are helpful in the diagnosis of NAFLD/NASH, but a liver biopsy is often required for definitive diagnosis. Many new plasma biomarkers and imaging techniques are now available that should improve the ability to diagnose NAFLD noninvasively Due to its complexity and extrahepatic complications, treatment of NAFLD requires a multidisciplinary approach with excellent preventative care, management, and treatment. This review will evaluate our current understanding of NAFLD, with a focus on existing therapeutic approaches and potential pharmacological developments.

scholarly journals Therapeutic effect and autophagy regulation of myriocin in nonalcoholic steatohepatitis

2019 ◽  
Vol 18 (1) ◽  
Author(s):  
Rui-Xu Yang ◽  
Qin Pan ◽  
Xiao-Lin Liu ◽  
Da Zhou ◽  
Feng-Zhi Xin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Biopsy ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
De Novo ◽  
Sprague Dawley ◽  
Nonalcoholic Fatty Liver ◽  
Sprague Dawley Rats ◽  
Serum Transaminases ◽  
Lobular Inflammation

Abstract Background Ceramide plays pathogenic roles in nonalcoholic fatty liver disease (NAFLD) via multiple mechanisms, and as such inhibition of ceramide de novo synthesis in the liver may be of therapeutically beneficial in patients with NAFLD. In this study, we aimed to explore whether inhibition of ceramide signaling by myriocin is beneficial in animal model of NAFLD via regulating autophagy. Methods Sprague Dawley rats were randomly divided into three groups: standard chow (n = 10), high-fat diet (HFD) (n = 10) or HFD combined with oral administration of myriocin (0.3 mg/kg on alternate days for 8 weeks) (n = 10). Liver histology and autophagy function were measured. HepG2 cells were incubated with fatty acid with or without myriocin treatment. Lipid accumulation and autophagy markers in the HepG2 cells were analyzed. Serum ceramide changes were studied in 104 subjects consisting healthy adults, liver biopsy-proven patients with NAFLD and liver biopsy-proven patients with chronic hepatitis B (CHB). Results Myriocin reversed the elevated body weight and serum transaminases and alleviated dyslipidemia in HFD fed rats. Myriocin treatment significantly attenuated liver pathology including steatosis, lobular inflammation and ballooning. By qPCR analysis, it was revealed that myriocin corrected the expression pattern of fatty acid metabolism associated genes including Fabp1, Pparα, Cpt-1α and Acox-2. Further, myriocin also restored the impaired hepatic autophagy function in rats with HFD-induced NASH, and this has been verified in HepG2 cells. Among the sphingolipid species that we screened in lipidomic profiles, significantly increased ceramide was observed in NASH patients as compared to the controls and non-NASH patients, regardless of whether or not they have active CHB. Conclusions Ceramide may play an important regulatory role in the autophagy function in the pathogenesis of NASH. Hence, blockade of ceramide signaling by myriocin may be of therapeutically beneficial in NASH. Trial registration Registration ID: ChiCTR-DDT-13003983. Data of registration: 13 May, 2013, retrospectively registered.

scholarly journals Role of X-Box Binding Protein-1 in Fructose-Induced De Novo Lipogenesis in HepG2 Cells

2018 ◽  
Vol 131 (19) ◽  
pp. 2310-2319
Author(s):  
Xian Yu ◽  
Lu-Ping Ren ◽  
Chao Wang ◽  
Ya-Jun Zhu ◽  
Han-Ying Xing ◽  
...  
Keyword(s):  
Hepg2 Cells ◽  
De Novo ◽  
Binding Protein ◽  
De Novo Lipogenesis

Growth hormone ameliorates high glucose-induced steatosis on in vitro cultured human HepG2 hepatocytes by inhibiting de novo lipogenesis via ChREBP and FAS suppression

2020 ◽  
Vol 53-54 ◽  
pp. 101332
Author(s):  
Eréndira Villanueva-Ortega ◽  
Lucia A. Méndez-García ◽  
Guadalupe N. Garibay-Nieto ◽  
Estibalitz Laresgoiti-Servitje ◽  
Patricia Medina-Bravo ◽  
...  
Keyword(s):  
Growth Hormone ◽  
High Glucose ◽  
De Novo ◽  
De Novo Lipogenesis

Identification and function of phosphorylation in the glucose-regulated transcription factor ChREBP

2008 ◽  
Vol 411 (2) ◽  
pp. 261-270 ◽  
Author(s):  
Nikolas G. Tsatsos ◽  
Michael N. Davies ◽  
Brennon L. O'callaghan ◽  
Howard C. Towle
Keyword(s):  
Transcription Factor ◽  
High Glucose ◽  
Leucine Zipper ◽  
De Novo ◽  
Regulatory Region ◽  
De Novo Lipogenesis ◽  
Nuclear Accumulation ◽  
Helix Loop Helix ◽  
Genes Encoding ◽  
And Function

In the liver, induction of genes encoding enzymes involved in de novo lipogenesis occurs in response to increased glucose metabolism. ChREBP (carbohydrate-response-element-binding protein) is a basic helix–loop–helix/leucine zipper transcription factor that regulates expression of these genes. To evaluate the potential role of ChREBP phosphorylation in its regulation, we used MS to identify modified residues. In the present paper, we report the detection of multiple phosphorylation sites of ChREBP expressed in hepatocytes, several of which are only observed under high-glucose conditions. Mutation of each of these serine/threonine residues of ChREBP did not alter its ability to respond to glucose. However, mutation of five N-terminal phosphoacceptor sites resulted in a major decrease in activity under high-glucose conditions. These phosphorylated residues are located within a region of ChREBP (amino acids 1–197) that is critical for glucose regulation. Mutation of Ser56 within this region to an aspartate residue resulted in increased nuclear accumulation and activity under high-glucose conditions. Together, these data suggest that ChREBP activity is regulated by complex multisite phosphorylation patterns involving its N-terminal regulatory region.

scholarly journals Suppressed de novo lipogenesis by plasma membrane citrate transporter inhibitor promotes apoptosis in HepG2 cells

FEBS Open Bio ◽  
2018 ◽  
Vol 8 (6) ◽  
pp. 986-1000 ◽  
Author(s):  
Phornpun Phokrai ◽  
Wan‐angkan Poolsri ◽  
Somrudee Suwankulanan ◽  
Narinthorn Phakdeeto ◽  
Worasak Kaewkong ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Hepg2 Cells ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Citrate Transporter

scholarly journals Epistructured catechins, EGCG and EC facilitate apoptosis induction through targeting de novo lipogenesis pathway in HepG2 cells

2018 ◽  
Vol 18 (1) ◽  
Author(s):  
Phuriwat Khiewkamrop ◽  
Pattamaphron Phunsomboon ◽  
Lysiane Richert ◽  
Dumrongsak Pekthong ◽  
Piyarat Srisawang
Keyword(s):  
Hepg2 Cells ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
Apoptosis Induction

scholarly journals Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases

2021 ◽  
Vol 45 (5) ◽  
pp. 655-674
Author(s):  
Inês Sousa-Lima ◽  
Hyun Jeong Kim ◽  
John Jones ◽  
Young-Bum Kim
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Liver Diseases ◽  
De Novo ◽  
Rho Kinase ◽  
De Novo Lipogenesis ◽  
Major Public Health Problem ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Lipid

Nonalcoholic fatty liver disease (NAFLD) is a major public health problem and the most common form of chronic liver disease, affecting 25% of the global population. Although NAFLD is closely linked with obesity, insulin resistance, and type 2 diabetes mellitus, knowledge on its pathogenesis remains incomplete. Emerging data have underscored the importance of Rho-kinase (Rho-associated coiled-coil-containing kinase [ROCK]) action in the maintenance of normal hepatic lipid homeostasis. In particular, pharmacological blockade of ROCK in hepatocytes or hepatic stellate cells prevents the progression of liver diseases such as NAFLD and fibrosis. Moreover, mice lacking hepatic ROCK1 are protected against obesity-induced fatty liver diseases by suppressing hepatic de novo lipogenesis. Here we review the roles of ROCK as an indispensable regulator of obesity-induced fatty liver disease and highlight the key cellular pathway governing hepatic lipid accumulation, with focus on de novo lipogenesis and its impact on therapeutic potential. Consequently, a comprehensive understanding of the metabolic milieu linking to liver dysfunction triggered by ROCK activation may help identify new targets for treating fatty liver diseases such as NAFLD.

Sign in / Sign up

Export Citation Format

Share Document