scholarly journals Mechanism of the Inhibitory Effects ofEucommia ulmoidesOliv. Cortex Extracts (EUCE) in the CCl4-Induced Acute Liver Lipid Accumulation in Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-11 ◽  
Author(s):  
Chang-Feng Jin ◽  
Bo Li ◽  
Shun-Mei Lin ◽  
Raj-Kumar Yadav ◽  
Hyung-Ryong Kim ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Liver Lipid ◽  
Eucommia Ulmoides ◽  
Dependent Manner ◽  
Protective Effects ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Er Stress Response ◽  
Acute Injection

Eucommia ulmoidesOliv. (EU) has been used for treatment of liver diseases. The protective effects ofEucommia UlmoidesOliv. cortex extracts (EUCE) on the carbon tetrachloride- (CCl4-) induced hepatic lipid accumulation were examined in this study. Rats were orally treated with EUCE in different doses prior to an intraperitoneal injection of 1 mg/kg CCl4. Acute injection of CCl4decreased plasma triglyceride but increased hepatic triglyceride and cholesterol as compared to control rats. On the other hand, the pretreatment with EUCE diminished these effects at a dose-dependent manner. CCl4treatment decreased glutathione (GSH) and increased malondialdehyde (MDA) accompanied by activated P450 2E1. The pretreatment with EUCE significantly improved these deleterious effects of CCl4. CCl4treatment increased P450 2E1 activation and ApoB accumulation. Pretreatment with EUCE reversed these effects. ER stress response was significantly increased by CCl4, which was inhibited by EUCE. One of the possible ER stress regulatory mechanisms, lysosomal activity, was examined. CCl4reduced lysosomal enzymes that were reversed with the EUCE. The results indicate that oral pretreatment with EUCE may protect liver against CCl4-induced hepatic lipid accumulation. ER stress and its related ROS regulation are suggested as a possible mechanism in the antidyslipidemic effect of EUCE.

Ixeris dentata Decreases ER Stress and Hepatic Lipid Accumulation through Regulation of ApoB Secretion

2014 ◽  
Vol 42 (03) ◽  
pp. 639-649 ◽  
Author(s):  
Mi-Rin Lee ◽  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Hye-Kyung Kim ◽  
Nan-Young Kim ◽  
...  
Keyword(s):  
Stress Response ◽  
Er Stress ◽  
Lipid Accumulation ◽  
Herbal Remedy ◽  
Saturated Fatty Acids ◽  
Initiation Factor ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Er Stress Response ◽  
Ixeris Dentata

Nonalcoholic fatty liver disease (NAFLD) is caused by the hepatic accumulation of saturated fatty acids involving the ER stress mechanism. Secretion of apo lipid carrier proteins and their binding to hepatic TG and cholesterol are affected by ER stress. This study was designed to identify ER stress regulators with potential effects against hepatic lipid accumulation. Ixeris dentata (IXD) is a traditional herbal remedy for indigestion, hepatitis, and diabetes used in Korea, Japan, and China. To examine the regulatory effects of IXD against hepatic lipid accumulation and elucidate its suggested mechanism of ER stress, HepG2 hepatocytes were treated with IXD extract in the presence of palmitate. While palmitate induced an ER stress response in hepatocytes, as indicated by the upregulation of PERK, increased eukaryotic initiation factor 2α (eIF2α) phosphorylation, enhanced expression of GADD153/C/EBP homologous protein (CHOP), and reduced secretion of apoB resulting in hepatic cellular accumulation of triglycerides (TG) and cholesterol, IXD extract significantly inhibited the lipid accumulation and PERK/eIF2α/CHOP-axis of the ER stress response. The inhibition of the PERK/eIF2α/CHOP signaling pathway by IXD in palmitate-treated cells suggests that IXD regulates hepatic dyslipidemia through the regulation of ER stress.

scholarly journals Eucommia ulmoides Oliver Extract, Aucubin, and Geniposide Enhance Lysosomal Activity to Regulate ER Stress and Hepatic Lipid Accumulation

PLoS ONE ◽  
2013 ◽  
Vol 8 (12) ◽  
pp. e81349 ◽  
Author(s):  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Mi-Rin Lee ◽  
Hye-Kyung Kim ◽  
Nan-young Kim ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Eucommia Ulmoides ◽  
Lysosomal Activity ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Eucommia Ulmoides Oliver

The role of increased FGF21 in VLDL-TAG secretion and thermogenic gene expression in mice under protein malnutrition

2021 ◽  
Author(s):  
Yori Ozaki-Masuzawa ◽  
Hiroki Kosaka ◽  
Rino Abiru ◽  
Yumiko Toda ◽  
Kota Kawabata ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Accumulation ◽  
Liver Lipid ◽  
Protective Role ◽  
Protein Malnutrition ◽  
Fibroblast Growth Factor 21 ◽  
Dependent Manner ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Abstract Protein malnutrition promotes hepatic lipid accumulation in growing animals. In these animals, fibroblast growth factor 21 (FGF21) rapidly increases in the liver and circulation and plays a protective role in hepatic lipid accumulation. To investigate the mechanism by which FGF21 protects against liver lipid accumulation under protein malnutrition, we determined whether upregulated FGF21 promotes thermogenesis or secretion of very-low-density lipoprotein (VLDL)–triacylglycerol (TAG). The results showed that protein malnutrition decreased VLDL-TAG secretion, but upregulation of FGF21 did not oppose this effect. In addition, protein malnutrition increased expression of the thermogenic gene uncoupling protein 1 in inguinal white adipose and brown adipose tissue in an FGF21-dependent manner. However, surgically removing inguinal white adipose tissue did not affect liver triglyceride levels in protein-malnourished mice. These data suggest that FGF21 stimulates thermogenesis under protein malnutrition, but this is not the causative factor underlying the protective role of FGF21 against liver lipid accumulation.

Abstract 540: Activation of Srebp1c Processing is Required in Flx-Induced Hepatic Lipid Accumulation

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Jing Xiong
Keyword(s):  
Lipid Accumulation ◽  
Proteolytic Cleavage ◽  
Mild Stress ◽  
Dependent Manner ◽  
Proteolytic Activation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Primary Mouse ◽  
Mouse Hepatocytes ◽  
Liver Tissues

Fluoxetine (FLX), a typical drug belonging to the category of selective serotonin reuptake inhibitors (SSRI), is the most widely prescribed psychoactive drug in the treatment of depression and other mood disorders. It has been demonstrated that the administration of FLX increases the possibility of weight gain and dyslipidemia. We find previously that dysregulation of lipogenic and lipolytic genes is critical in FLX-promoted hepatic lipid accumulation. Therefore, a chronic mild stress depression model and cultured primary mouse hepatocytes were used to investigate the effects and underlying mechanisms of FLX on the promoted hepatic lipid accumulation. The evidence have shown that FLX increases the concentrations of triglyceride (TG) and total cholesterol (TC) in the liver tissues of depressive mice, while only increases TG in the liver tissues of normal mice. FLX induces lipid accumulation in both normal and depressive mice by upregulating the lipogeneic genes Acetyl-CoA carboxylase 1 (ACC1) and Fatty acid synthase (FAS) expression and downregulating the lipolytic genes carboxylesterase 1 (CES1) and CES2. Using primary cultured mouse hepatocytes, it is shown that FLX promotes the expression of transcription factor SREBP1c as well as its proteolytic cleavage and nuclear translocation. FLX significantly suppresses SREBP1c proteolytic cleavage in hepatocytes after the incubation lasting as short as 3 hours, which is a more prompt way than the elevated expression of SREBP1c. Further experiments show that the specific inhibitors of proteases S1P and S2P attenuate FLX-induced SREBP1c activation and hepatic lipid accumulation. As SCAP (SREBP cleavage-activating protein) escorts SREBPs from the endoplasmic reticulum to the Golgi complex where proteases cleave SREBPs and therefore is required for SREBP activation, we find that FLX promotes the protein level of SCAP in a concentration- and time-dependent manner. In conclusion, FLX directly acts on the hepatocytes by facilitating the expression and proteolytic activation of SREBP1c to promote hepatic lipid accumulation. The findings not only provide new insight into the understanding of the mechanisms for SSRI-mediated dyslipidemia effects, but also suggest a novel therapeutic target to interfere.

scholarly journals Protective effects of farnesoid X receptor (FXR) on hepatic lipid accumulation are mediated by hepatic FXR and independent of intestinal FGF15 signal

2014 ◽  
Vol 35 (4) ◽  
pp. 1133-1144 ◽  
Author(s):  
Johannes Schmitt ◽  
Bo Kong ◽  
Bruno Stieger ◽  
Oliver Tschopp ◽  
Simon M. Schultze ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Farnesoid X Receptor ◽  
Protective Effects ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

scholarly journals R. verniciflua and E. ulmoides Extract (ILF-RE) Protects against Chronic CCl4-Induced Liver Damage by Enhancing Antioxidation

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 382 ◽  
Author(s):  
Hwa-Young Lee ◽  
Geum-Hwa Lee ◽  
Young Yoon ◽  
Han-Jung Chae
Keyword(s):  
Oxidative Stress ◽  
Er Stress ◽  
Liver Damage ◽  
Lipid Accumulation ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Protective Effects ◽  
Gamma Glutamyl Transpeptidase ◽  
Hepatic Lipid Accumulation ◽  
Lipogenic Genes

This study aimed to characterize the protective effects of R. verniciflua extract (ILF-R) and E. ulmoides extract (ILF-E), the combination called ILF-RE, against chronic CCl4-induced liver oxidative injury in rats, as well as to investigate the mechanism underlying hepatoprotection by ILF-RE against CCl4-induced hepatic dysfunction. Chronic hepatic stress was induced via intraperitoneal (IP) administration of a mixture of CCl4 (0.2 mL/100 g body weight) and olive oil [1:1(v/v)] twice a week for 4 weeks to rats. ILF-RE was administered orally at 40, 80, and 120 mg/kg to rats for 4 weeks. Alanine transaminase (ALT), aspartate transaminase (AST), gamma-glutamyl transpeptidase (GGT), and lipid peroxidation assays were performed, and total triglyceride, cholesterol, and LDL-cholesterol levels were quantified. Furthermore, ER stress and lipogenesis-related gene expression including sterol regulatory element-binding transcription factor 1 (SREBP-1), fatty acid synthase (FAS), and P-AMPK were assessed. ILF-RE markedly protected against liver damage by inhibiting oxidative stress and increasing antioxidant enzyme activity including glutathione (GSH), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase. Furthermore, hepatic dyslipidemia was regulated after ILF-RE administration. Moreover, hepatic lipid accumulation and its associated lipogenic genes, including those encoding SREBP-1 and FAS, were regulated after ILF-RE administration. This was accompanied by regulation of ER stress response signaling, suggesting a mechanism underlying ILF-RE-mediated hepatoprotection against lipid accumulation. The present results indicate that ILF-RE exerts hepatoprotective effects against chronic CCl4-induced dysfunction by suppressing hepatic oxidative stress and lipogenesis, suggesting that ILF-RE is a potential preventive/therapeutic natural product in treating hepatoxicity and associated dysfunction.

scholarly journals Caffeine reduces hepatic lipid accumulation through regulation of lipogenesis and ER stress in zebrafish larvae

2015 ◽  
Vol 22 (1) ◽  
Author(s):  
Xinchun Zheng ◽  
Wencong Dai ◽  
Xiaohui Chen ◽  
Kunyuan Wang ◽  
Wenqing Zhang ◽  
...  
Keyword(s):  
Er Stress ◽  
Lipid Accumulation ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Zebrafish Larvae

scholarly journals t10,c12-CLA decreases adiposity in peripubertal mice without dose-related detrimental effects on mammary development, inflammation status, and metabolism

2010 ◽  
Vol 299 (6) ◽  
pp. R1521-R1528 ◽  
Author(s):  
M. R. Foote ◽  
S. L. Giesy ◽  
G. Bernal-Santos ◽  
D. E. Bauman ◽  
Y. R. Boisclair
Keyword(s):  
Lipid Accumulation ◽  
Inflammatory Responses ◽  
Mouse Mammary Gland ◽  
Mammary Development ◽  
Dependent Manner ◽  
Negative Effects ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation ◽  
Ductal Hyperplasia ◽  
Igf Binding

The trans 10, cis 12-conjugated linoleic acid (10,12-CLA) isomer reduces adiposity in several animal models. In the mouse, however, this effect is associated with adipose tissue inflammation, hyperinsulinemia and hepatic lipid accumulation. Moreover, 10,12-CLA was recently shown to promote mammary ductal hyperplasia and ErbB2/Her2-driven mammary cancer in the mouse. Reasons for detrimental effects of 10,12-CLA on the mouse mammary gland could relate to its effect on the mammary fat pad (MFP), which is essential for normal development. Accordingly, we hypothesized that mammary effects of 10,12-CLA were mediated through the MFP in a dose-dependent manner. Female FVB mice were fed 10,12-CLA at doses of 0%, 0.1%, 0.2%, or 0.5% of the diet from day 24 of age, and effects on mammary development and metabolism were measured on day 49. The 0.5% dose reduced ductal elongation and caused premature alveolar budding. These effects were associated with increased expression of inflammatory markers and genes shown to alter epithelial growth (IGF binding protein-5) and alveolar budding (TNF-α and receptor of activated NF-κB ligand). The 0.5% dose also caused hyperinsulinemia and hepatic lipid accumulation. In contrast, the 0.1% 10,12-CLA dose had no adverse effects on mammary development, metabolic events, and inflammatory responses, but remained effective in decreasing adipose weights and lipogenic gene expression. These results show that a low dose of 10,12 -CLA reduces adiposity in the mouse without negative effects on mammary development, inflammation, and metabolism, and suggest that previously reported detrimental effects relate to the use of excessive doses.

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