Chalcones suppress fatty acid-induced lipid accumulation through a LKB1/AMPK signaling pathway in HepG2 cells

2014 ◽  
Vol 5 (6) ◽  
pp. 1134-1141 ◽  
Author(s):  
Tianshun Zhang ◽  
Norio Yamamoto ◽  
Hitoshi Ashida
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Ampk Signaling

Excessive lipid accumulation in the liver has been proposed to cause hyperlipidemia, diabetes and fatty liver disease.

scholarly journals Apigenin Alleviates Non-Alcoholic Fatty Liver Disease by Downregulating the NLRP3/NF-κB Signaling Pathway in Mice

2021 ◽  
Author(s):  
Zheng Lu ◽  
Lu Liu ◽  
Shunxin Zhao ◽  
Jiangtao Zhao ◽  
Sujun Li
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract Background: Apigenin, a flavone found in several plant foods with various biological properties including anti-inflammatory and other abilities, alleviated non-alcohol fatty liver disease (NAFLD) induced by a high fat diet (HFD) in mice. However, the mechanisms underlying this protection of inflammation and NAFLD has not been known clearly. Methods: Low density lipoprotein receptor-deficient (Ldlr-/-) mice were fed with HFD diet to induce NAFLD model and were treated with apigenin (50 mg/kg/day) for eight weeks. Hepatic lipid accumulation and inflammation in the livers were analyzed and quantified. In vitro experiments, HepG2 cells were stimulated by LPS plus oleic acid (OA) in the absence of presence of apigenin (50μM). Lipid accumulation and the effect of apigenin on NLRP3/NF-κB signaling pathway was investigated.Results: Apigenin administration reduce the weight, plasma lipid levels in Ldlr-/- mice when fed an HFD. Apigenin (50 mg/kg/day) treated mice displayed reduced hepatic lipid accumulation and inflammation in the livers of mice given the HFD diet. Treating the HepG2 cells with apigenin reduced lipid accumulation. And, apigenin also inhibited activation of NLRP3/NF-κB signaling pathway stimulated by OA together with LPS. Conclusions: Our results indicated that apigenin supplementation prevented NAFLD via down-regulating the NLRP3/NF-κB signaling pathway in mice, and suggested apigenin might be a potential therapeutic agent for the prevention of NAFLD.

scholarly journals SGL 121 Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism Through AMPK Signaling Pathway

2020 ◽  
Vol 21 (12) ◽  
pp. 4534
Author(s):  
Da Eun Kim ◽  
Bo Yoon Chang ◽  
Byeong Min Jeon ◽  
Jong In Baek ◽  
Sun Chang Kim ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Density Lipoprotein ◽  
Nonalcoholic Fatty Liver

A ginsenoside F2-enhanced mixture (SGL 121) increases the content of ginsenoside F2 by biotransformation. In the present study, we investigated the effect of SGL 121 on nonalcoholic fatty liver disease (NAFLD) in vitro and in vivo. High-fat, high-carbohydrate-diet (HFHC)-fed mice were administered SGL 121 for 12 weeks to assess its effect on improving NAFLD. In HepG2 cells, SGL 121 acted as an antioxidant, a hepatoprotectant, and had an anti-lipogenic effect. In NAFLD mice, SGL 121 significantly improved body fat mass; levels of hepatic triglyceride (TG), hepatic malondialdehyde (MDA), serum total cholesterol (TC), high-density lipoprotein (HDL), and low-density lipoprotein (LDL); and activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). In HepG2 cells, induced by oxidative stress, SGL 121 increased cytoprotection, inhibited reactive oxygen species (ROS) production, and increased antioxidant enzyme activity. SGL 121 activated the Nrf2/HO-1 signaling pathway and improved lipid accumulation induced by free fatty acids (FFA). Sterol regulatory element-binding protein-1 (SREBP-1) and fatty acid synthase (FAS) expression was significantly reduced in NAFLD-induced liver and HepG2 cells treated with SGL 121. Moreover, SGL 121 activated adenosine monophosphate-activated protein kinase (AMPK), which plays an important role in the regulation of lipid metabolism. The effect of SGL 121 on the improvement of NAFLD seems to be related to its antioxidant effects and activation of AMPK. In conclusion, SGL 121 can be potentially used for the treatment of NAFLD.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yu ◽  
Xi Xu ◽  
Jing Zhang ◽  
Xuan Xia ◽  
Fen Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

scholarly journals Dietary Blueberry and Bifidobacteria Attenuate Nonalcoholic Fatty Liver Disease in Rats by Affecting SIRT1-Mediated Signaling Pathway

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Tingting Ren ◽  
Chao Huang ◽  
Mingliang Cheng
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Control Group ◽  
Nonalcoholic Fatty Liver ◽  
Blueberry Juice ◽  
Group A ◽  
Better Than

NAFLD model rats were established and divided into NAFLD model (MG group), SIRT1 RNAi (SI group), blueberry juice (BJ group), blueberry juice + bifidobacteria (BJB group), blueberry juice + SIRT1 RNAi (BJSI group), and blueberry juice + bifidobacteria + SIRT1 RNAi groups (BJBSI group). A group with normal rats was a control group (CG). BJB group ameliorated NAFLD, which was better than BJ group (P<0.05). The lipid accumulation was lower in CG, BJ, and BJB groups than that in MG, SI, BJSI, and BJBSI groups (P<0.05). The levels of SIRT1 and PPAR-αwere higher in CG, BJ, and BJB groups than those in MG, SI, BJSI, and BJBSI groups (P<0.05). The levels of SREBP-1c were lower in CG, BJ, and BJB groups than those in MG, SI, BJSI, and BJBSI groups (P<0.05). The biochemical indexes SOD, GSH, and HDL-c were improved from CG to BJB group (P<0.05). Inversely, the levels of AST and ALT, TG, TC, LDL-c, and MDA were decreased from CG to BJB group (P<0.05). These changes enhance antioxidative capability and biochemical index of rats. Blueberry juice and bifidobacteria improve NAFLD by activating SIRTI-mediating signaling pathway.

scholarly journals Niacin Ameliorates Hepatic Steatosis by Inhibiting De Novo Lipogenesis Via a GPR109A-Mediated PKC–ERK1/2–AMPK Signaling Pathway in C57BL/6 Mice Fed a High-Fat Diet

2019 ◽  
Vol 150 (4) ◽  
pp. 672-684 ◽  
Author(s):  
Lingyan Ye ◽  
Zheng Cao ◽  
Xiangru Lai ◽  
Ying Shi ◽  
Naiming Zhou
Keyword(s):  
Liver Disease ◽  
Protein Kinase ◽  
Fatty Liver ◽  
Signaling Pathway ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Hepg2 Cells ◽  
De Novo ◽  
De Novo Lipogenesis ◽  
High Fat

ABSTRACT Background Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease in the world. Hepatic de novo lipogenesis (DNL) has been suggested to contribute to the pathogenesis of NAFLD. Recent studies have demonstrated that niacin (NA) modulates hepatic DNL through GPR109A. However, the underlying mechanism remains largely unknown. Objectives This study aims to elucidate the potential molecular mechanism by which GPR109A inhibits hepatic DNL. Methods C57BL/6 wild-type (WT) and Gpr109a knockout (KO) mice (male, 5 wk old) were fed a high-fat diet (60% energy from fat) firstly for 6 wk to generate a diet-induced obese model. Subsequently, they were randomly divided into 4 groups for the next 8–9 wk: WT mice with oral water [WT + vehile (VE)], WT mice with oral NA (50 mM, dissolved in water) (WT + NA), KO mice with oral water (KO + VE), and KO mice with oral NA (50 mM) (KO + NA). Mechanisms were examined in HepG2 cells. Body composition, liver histology, biomarkers of hepatic function, lipid accumulation, and lipid synthesis signals in HepG2 cells were measured. Results Upon activation, GPR109A apparently protected against obesity and hepatic steatosis (P &lt; 0.05). The concentrations of hepatic Tnf-α in the WT + NA group were about 50% of those in the WT + VE group (P &lt; 0.05). The activities of serum alanine transaminase and aspartate transaminase were 26.7% and 53.5% lower in the WT + NA group than in the WT + VE group, respectively (P &lt; 0.05). In HepG2 cells, activation of GPR109A resulted in remarkable inhibition of oleic acid–induced lipid accumulation via a protein kinase C–extracellular signal-regulated kinase-1/2–AMP-activated protein kinase signaling pathway. Conclusions NA inhibits hepatic lipogenesis in C57BL/6 mice through a GPR109A-mediated signaling pathway, consistent with the mechanistic studies in HepG2 cells, suggesting its potential for treatment of NAFLD and other fatty liver diseases.

Silibinin Ameliorates Fructose-induced Lipid Accumulation and Activates Autophagy in HepG2 Cells

2019 ◽  
Vol 19 (5) ◽  
pp. 632-642 ◽  
Author(s):  
Yang Li ◽  
Luping Ren ◽  
Guangyao Song ◽  
Pu Zhang ◽  
Liying Yang ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Light Chain ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
High Fructose

Background: Autophagy was recently regarded as a potential mechanism in nonalcoholic fatty liver disease. Silibinin (SIL), a natural flavonoid, has been used to prevent nonalcoholic fatty liver disease, however, the underlying mechanism is unclear. The aim of the present study was to explore the effect of SIL on hepatic steatosis and the possible link with autophagy. Methods: The degree of hepatic steatosis in HepG2 cells was observed by oil-red O staining and triglyceride content. The effect of SIL on autophagy was tested by the Autophagy Detection Kit, and the expression of sterol regulatory element binding protein 1 (srebp-1), Fatty Acid Synthase (Fas), light chain 3, beclin-1, p62, AMP-activated Kinase (AMPK), and mammalian Target Of Rapamycin (mTOR) was examined by western blots. Results: The lipid accumulation of HepG2 cells increased significantly in the high-fructose group compared to the control group. After SIL intervention, lipid accumulation was decreased. Using a fluorescence microscope, SIL was found to induce autophagy. Compared to control, the expressions of srebp-1, Fas, and phosphorylated-mTOR were increased by high-fructose, while the expressions of light chain 3 and beclin-1 decreased and srebp-1, Fas, and p62 were increased by autophagy inhibition. In contrast, opposite results were found in the SIL intervention group. The protein content of phosphorylated- mTOR was decreased, while phosphorylated-AMPK was increased in the SIL group compared to the high-fructose group. Conclusion: SIL can reduce lipid accumulation in HepG2 cells exposed to high-fructose by inducing autophagy. The AMPK/mTOR signaling pathway could be one of the underlying molecular mechanisms.

scholarly journals A microfluidic patterned model of non-alcoholic fatty liver disease: applications to disease progression and zonation

Lab on a Chip ◽  
2019 ◽  
Vol 19 (18) ◽  
pp. 3022-3031 ◽  
Author(s):  
Beyza Bulutoglu ◽  
Camilo Rey-Bedón ◽  
Young Bok (Abraham) Kang ◽  
Safak Mert ◽  
Martin L. Yarmush ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Free Fatty Acid ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
Fatty Liver Disease ◽  
Wide Spectrum ◽  
Progressive Increase ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) involves a progressive increase of lipid accumulation. We created a microfluidic progressive NAFLD platform using free fatty acid gradients to capture the wide spectrum of disease conditions in a single continuous liver tissue.

scholarly journals 5-ALA ameliorates hepatic steatosis through AMPK signaling pathway

2017 ◽  
Vol 59 (2) ◽  
pp. 121-128 ◽  
Author(s):  
Haoyong Yu ◽  
Mingliang Zhang ◽  
Yunqin Ma ◽  
Junxi Lu ◽  
Jiemin Pan ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Signaling Pathway ◽  
Fatty Liver Disease ◽  
Aminolevulinic Acid ◽  
Therapeutic Effects ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

5-Aminolevulinic acid (5-ALA), the first compound in the porphyrin synthesis pathway, has been reported to ameliorate the diabetic state in Otsuka Long-Evans Tokushima Fatty rats by reducing fat pad weight in the retroperitoneal region. Dietary supplementation with 5-ALA has additionally demonstrated the capacity to lower blood glucose and HbA1c levels among subjects with diabetes. The etiology of nonalcoholic fatty liver disease (NAFLD) is complex and its typical characteristics include obesity and insulin resistance. As 5-ALA supplementation has previously normalized glucose and insulin resistance, we sought to investigate whether 5-ALA had potential therapeutic effects on NAFLD and elucidate the signal pathway mediating these effects. To explore these questions, we fed C57BL/6J mice a high-fat diet (HFD) to induce a fatty liver disease and supplemented the diet-induced obese (DIO) mice with 5-ALA. The mice in the presence of 5-ALA demonstrated a decrease in body weight and hepatic lipid content and moderate improvement in glucose homeostasis compared to untreated controls. Further, we found that 5-ALA activated AMPK signaling pathway, which was correlated with enhanced lipolysis and fatty acid β-oxidation. Human hepatocarcinoma cells (HepG2 cells) treated with 5-ALA were additionally used to investigate the mechanics of 5-ALA. Treated cells had a higher expression of lipolysis-related genes, including PGC-1α. Our data indicated that 5-ALA might represent a novel compound that could be useful for the treatment of nonalcoholic fatty liver disease (NAFLD), likely through the restoration of phosphorylation levels of AMPK (Thr172) and acetyl-CoA (ACC) (Ser79), further enhanced PGC1α and CPT1α expression.

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