scholarly journals Nobiletin Inhibits Hepatic Lipogenesis via Activation of AMP-Activated Protein Kinase

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Taewon Yuk ◽  
Younghwa Kim ◽  
Jinwoo Yang ◽  
Jeehye Sung ◽  
Heon Sang Jeong ◽  
...  
Keyword(s):  
Protein Kinase ◽  
High Glucose ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Hepatic Lipogenesis ◽  
Nonalcoholic Fatty Liver ◽  
Compound C ◽  
Amp Activated Protein Kinase

We aimed to investigate the effects of nobiletin on hepatic lipogenesis in high glucose-induced lipid accumulation in HepG2 cells. Nobiletin, a citrus polymethoxyflavonoid with six methoxy groups, is present abundantly in the peels of citrus fruits. HepG2 cells were incubated in Dulbecco’s modified Eagle’s medium containing high glucose (25 mM) and subsequently treated with nobiletin at different concentrations (5, 25, and 50 μM). Results showed that nobiletin markedly inhibited high glucose-induced hepatic lipid accumulation in HepG2 cells. In addition, it reduced the protein expression of lipogenic factors, including sterol regulatory element-binding protein 1c (SREBP-1c) and fatty acid synthase (FAS). Nobiletin significantly increased the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Pretreatment with compound C, an AMPK inhibitor, abolished the inhibitory effects of nobiletin on SREBP-1c and FAS expression. These results suggested that nobiletin might attenuate high glucose-induced lipid accumulation in HepG2 hepatocytes via modulation of AMPK signaling pathway. Therefore, nobiletin might be useful for the prevention and treatment of nonalcoholic fatty liver diseases.

Houttuynia cordata Attenuates Lipid Accumulation via Activation of AMP-Activated Protein Kinase Signaling Pathway in HepG2 Cells

2014 ◽  
Vol 42 (03) ◽  
pp. 651-664 ◽  
Author(s):  
Hyun Kang ◽  
Sushruta Koppula
Keyword(s):  
Protein Kinase ◽  
High Glucose ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Molecular Mechanisms ◽  
Regulatory Element ◽  
Adenosine Monophosphate ◽  
Perennial Herb ◽  
Houttuynia Cordata

Houttuynia cordata (H. cordata) from the family Saururaceae is a perennial herb native to Southeast Asia. It possesses a range of medicinal properties to treat several disease symptoms including allergic inflammation and anaphylaxis. In the present investigation, we provided the molecular mechanisms underlying the role of H. cordata extract (HCE) in the prevention of high glucose-induced lipid accumulation in human HepG2 hepatocytes. HepG2 cells were pre-treated with various concentrations of HCE (0, 10, 20, 40, and 80 μg/mL) and treated with serum-free medium with normal glucose (5 mM) for 1 h, followed by exposure to high glucose (25 mM D-glucose) for 24 h. HCE significantly and dose-dependently attenuated lipid accumulation in human HepG2 hepatocytes when exposed to high glucose (25 mM D-glucose) (p < 0.05, p < 0.01 and p < 0.001 at 20, 40, and 80 μg/mL concentrations, respectively). Further, HCE attenuated the expression of fatty acid synthase (FAS), sterol regulatory element-binding protein-1 and glycerol 3-phosphate acyltransferases (GPATs). The adenosine monophosphate-activated protein kinase (AMPK) was also activated by HCE treatment when exposed to high glucose (25 mM D-glucose) in human HepG2 hepatocytes. This study suggests the hypolipidemic effects of HCE by the inhibition of lipid biosynthesis mediated through AMPK signaling, which may play an active role and can be developed as an anti-obesity agent.

scholarly journals Catalpol Attenuates Hepatic Steatosis by Regulating Lipid Metabolism via AMP-Activated Protein Kinase Activation

2020 ◽  
Vol 2020 ◽  
pp. 1-12 ◽  
Author(s):  
Xiang Tian ◽  
Qin Ru ◽  
Qi Xiong ◽  
Ruojian Wen ◽  
Yong Chen
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Target Genes ◽  
Dependent Manner ◽  
Compound C ◽  
Amp Activated Protein Kinase

The increased prevalence of nonalcoholic fatty liver disease (NAFLD), which develops from hepatic steatosis, represents a public health challenge. Catalpol, a natural component extracted from the roots of Radix Rehmanniae, has several pharmacological activities. The present study is aimed at examining whether catalpol prevents hepatic steatosis in cell and animal experiments and elucidating the possible mechanisms. HepG2 cells were treated with 300 μM palmitate (PA) and/or catalpol for 24 h in vitro, and male C57BL/6J mice fed a high-fat diet (HFD) were administered catalpol for 18 weeks in vivo. The results revealed that catalpol significantly decreased lipid accumulation in PA-treated HepG2 cells. Moreover, catalpol drastically reduced body weight and lipid accumulation in the liver, whereas it ameliorated hepatocyte steatosis in HFD-fed mice. Notably, catalpol remarkably promoted the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase. Subsequently, catalpol repressed the expressions of lipogenesis-associated genes such as sterol regulatory element-binding protein 1c and fatty acid synthase but promoted the expressions of genes associated with fatty acid β-oxidation such as peroxisome proliferator-activated receptor α together with its target genes carnitine palmitoyltransferase 1 and acyl-CoA oxidase 1 (ACOX1). However, the preincubation of the HepG2 cells with compound C (10 μM), an AMPK inhibitor, prevented catalpol-mediated beneficial effects. These findings suggest that catalpol ameliorates hepatic steatosis by suppressing lipogenesis and enhancing fatty acid β-oxidation in an AMPK-dependent manner. Therefore, catalpol has potential as a novel agent in the treatment of NAFLD.

Resveratrol ameliorates lipid accumulation in HepG2 cells, associated with down-regulation of lipin1 expression

2016 ◽  
Vol 94 (2) ◽  
pp. 185-189 ◽  
Author(s):  
Li Ying Tang ◽  
Yi Chen ◽  
Bei Bei Rui ◽  
Cheng Mu Hu
Keyword(s):  
Oleic Acid ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Regulatory Element ◽  
Control Group ◽  
Down Regulation ◽  
Alcoholic Fatty Liver ◽  
Compound C ◽  
Element Binding Protein ◽  
Amp Activated Protein Kinase

The pathogenesis of alcoholic fatty liver (AFL) disease is associated with the excessive accumulation of lipids in hepatocytes as well as oxidative stress. Resveratrol (RES), a dietary polyphenol found in red wine and grapes, has been shown to protect against AFL disease. However, the precise mechanisms that lead to this protective effect remain elusive. In this study, we used HepG2 cells to investigate the effects of RES on lipid metabolism and the mechanisms underlying these effects. HepG2 cells were cultured with oleic acid and alcohol for 48 h to induce excessive lipid accumulation. Oil red O staining showed that administration of oleic acid and alcohol induced more lipid accumulation than was observed in the control group, and that RES (15, 45, or 135 μmol/L) treatment reduced intracellular lipid droplets. RES treatment also significantly attenuated hepatic steatosis and lowered levels of intracellular triglycerides (TG). Western blot analysis showed that RES enhanced the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) and down-regulated the expression of sterol regulatory element-binding protein 1c (SREBP-1c) and lipin1. However, compound C, an AMPK inhibitor, reversed these effects of RES. In conclusion, RES reduced lipid accumulation and protected HepG2 cells. This effect may be associated with the down-regulation of SREBP-1c and lipin1 expression, increased levels of phosphorylated AMPK and ACC, and the activation of AMPK–lipin1 signaling.

scholarly journals Phloretin ameliorates hepatic steatosis through regulation of lipogenesis and Sirt1/AMPK signaling in obese mice

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Chian-Jiun Liou ◽  
Shu-Ju Wu ◽  
Szu-Chuan Shen ◽  
Li-Chen Chen ◽  
Ya-Ling Chen ◽  
...  
Keyword(s):  
Oleic Acid ◽  
Fatty Acid ◽  
Hepatic Steatosis ◽  
Lipid Accumulation ◽  
Hepg2 Cells ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Liver Lipid ◽  
Obese Mice ◽  
Alcoholic Fatty Liver

Abstract Background Phloretin is isolated from apple trees and could increase lipolysis in 3T3-L1 adipocytes. Previous studies have found that phloretin could prevent obesity in mice. In this study, we investigated whether phloretin ameliorates non-alcoholic fatty liver disease (NAFLD) in high-fat diet (HFD)-induced obese mice, and evaluated the regulation of lipid metabolism in hepatocytes. Methods HepG2 cells were treated with 0.5 mM oleic acid to induce lipid accumulation, and then treated with phloretin to evaluate the molecular mechanism of lipogenesis. In another experiment, male C57BL/6 mice were fed normal diet or HFD (60% fat, w/w) for 16 weeks. After the fourth week, mice were treated with or without phloretin by intraperitoneal injection for 12 weeks. Results Phloretin significantly reduced excessive lipid accumulation and decreased sterol regulatory element-binding protein 1c, blocking the expression of fatty acid synthase in oleic acid-induced HepG2 cells. Phloretin increased Sirt1, and phosphorylation of AMP activated protein kinase to suppress acetyl-CoA carboxylase expression, reducing fatty acid synthesis in hepatocytes. Phloretin also reduced body weight and fat weight compared to untreated HFD-fed mice. Phloretin also reduced liver weight and liver lipid accumulation and improved hepatocyte steatosis in obese mice. In liver tissue from obese mice, phloretin suppressed transcription factors of lipogenesis and fatty acid synthase, and increased lipolysis and fatty acid β-oxidation. Furthermore, phloretin regulated serum leptin, adiponectin, triglyceride, low-density lipoprotein, and free fatty acid levels in obese mice. Conclusions These findings suggest that phloretin improves hepatic steatosis by regulating lipogenesis and the Sirt-1/AMPK pathway in the liver.

AMP-activated protein kinase inhibits TGF-β-, angiotensin II-, aldosterone-, high glucose-, and albumin-induced epithelial-mesenchymal transition

2013 ◽  
Vol 304 (6) ◽  
pp. F686-F697 ◽  
Author(s):  
Jang Han Lee ◽  
Ji Hyun Kim ◽  
Ja Seon Kim ◽  
Jai Won Chang ◽  
Soon Bae Kim ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Protein Kinase ◽  
High Glucose ◽  
Renal Fibrosis ◽  
Epithelial Mesenchymal Transition ◽  
Urinary Albumin ◽  
Heme Oxygenase 1 ◽  
Mesenchymal Transition ◽  
Compound C ◽  
Amp Activated Protein Kinase

The epithelial-mesenchymal transition (EMT) is a novel mechanism that promotes renal fibrosis. Transforming growth factor-β (TGF-β), angiotensin II, aldosterone, high glucose, and urinary albumin are well-known causes of EMT and renal fibrosis. We examined whether and how activation of AMP-activated protein kinase (AMPK) suppressed EMT induced by the above agents in tubular epithelial cells. All experiments were performed using HK-2 cells. Protein expression was measured by Western blot analysis. Intracellular reactive oxygen species (ROS) were analyzed by flow cytometry. Exposure of tubular cells to TGF-β (10 ng/ml), angiotensin II (1 μM), aldosterone (100 nM), high glucose (30 mM), and albumin (5 mg/ml) for 5 days induced EMT, as shown by upregulation of α-smooth muscle actin and downregulation of E-cadherin. ROS and NADPH oxidase 4 (Nox4) expression were increased, and antioxidants such as tiron and N-acetylcysteine inhibited EMT induction. Metformin (the best known clinical activator of AMPK) suppressed EMT induction through inhibition of ROS via induction of heme oxygenase-1 and endogenous antioxidant thioredoxin. An AMPK inhibitor (compound C) and AMPK small interfering RNA blocked the effect of metformin, and another AMPK activator [5-aminoimidazole-4-carboxamide-1β riboside (AICAR)] exerted the same effects as metformin. In conclusion, AMPK activation might be beneficial in attenuating the tubulointerstitial fibrosis induced by TGF-β, angiotensin II, aldosterone, high glucose, and urinary albumin.

scholarly journals A High-Fat Diet Attenuates Amp-Activated Protein Kinase α1 in Adipocytes to Induce Exosome Shedding and Nonalcoholic Fatty Liver Development in Vivo

2020 ◽  
Author(s):  
Ada Admin ◽  
Chenghui Yan ◽  
Xiaoxiang Tian ◽  
Jiayin Li ◽  
Dan Liu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Kinase ◽  
Fatty Liver ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Liver Development ◽  
High Fat ◽  
Tissue Specific ◽  
Nonalcoholic Fatty Liver ◽  
Amp Activated Protein Kinase

Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (<a>AT</a>) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (<a>NAFLD</a>). Exosome components, liver fat content, and liver function were monitored in AT in mice fed a <a>high-fat diet </a>(<a>HFD</a>) or treated with metformin- or GW4869 and with AMP-activated protein kinase (AMPKα1)<i> </i>floxed<i> (Prkaα1</i><sup>fl/fl</sup>/WT), <a><i>Prkaα1</i><sup>-/-</sup></a>, liver tissue-specific <i>Prkaα1</i><sup>-/-</sup>, or AT-specific <i>Prkaα1</i><sup>-/-</sup> modification. In cultured adipocytes and white adipose tissue (WAT), the absence of <a><i>AMPKα1</i></a> increased exosome release and exosomal proteins by elevating <a>tumor susceptibility gene 101 (<i>TSG101</i></a>)-mediated exosome biogenesis. In adipocytes treated with palmitic acid, TSG101 facilitated scavenger receptor class B (CD36) sorting into exosomes. CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation. Consistently, an HFD induced more severe lipid accumulation and cell death in <a><i>Prkaα1</i><sup>-/-</sup> </a>and adipose tissue-specific <i>Prkaα1</i><sup>-/-</sup> mice than in WT and liver-specific <i>Prkaα1</i><sup>-/-</sup> mice. AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver specific <i>Prkaα1</i><sup>-/-</sup> mice. Moreover, administration of the exosome inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers in <i>Prkaα1</i><sup>-/-</sup> and adipocyte-specific <i>Prkaα1</i><sup>-/-</sup> mice. We conclude that HFD-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT C<a>D36</a>-containing exosomes.

scholarly journals Regulation of gene expression by glucose

1999 ◽  
Vol 58 (3) ◽  
pp. 621-623 ◽  
Author(s):  
P. Ferré
Keyword(s):  
Fatty Acid ◽  
Protein Kinase ◽  
Transcriptional Activation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Regulation Of Gene Expression ◽  
Acid Synthesis ◽  
Glucose Response ◽  
Amp Activated Protein Kinase ◽  
Fatty Acid Synthase Gene

Fatty acid synthase (EC 2.3.1.85) is an enzyme involved in the lipogenic pathway allowing fatty acid synthesis from glucose. Glucose up-regulates the transcription of the fatty acid synthase gene in both adipocytes and hepatocytes, with insulin having only an indirect role. The signal metabolite could be glucose-6-phosphate rather than glucose itself. The glucose response element of the fatty acid synthase gene has not yet been precisely identified, although a −2 kb region of the fatty acid synthase promoter is sufficient to confer nutritional responsiveness to a reporter gene. ADD1/SREBP1, a b-HLH-LZ transcription factor belonging to the sterol regulatory element-binding protein family might be involved in the transduction of the glucose effect. Finally, the stimulatory effect of glucose on the expression of the fatty acid synthase gene is inhibited by the activation of AMP-activated protein kinase. Interestingly enough, AMP-activated protein kinase is structurally and functionally related to the yeast SNF1 protein kinase complex which is essential for the transcriptional activation of glucose-repressed genes in Saccharomyces cerevisiae.

Sign in / Sign up

Export Citation Format

Share Document