scholarly journals Treatment with Ginger Ameliorates Fructose-Induced Fatty Liver and Hypertriglyceridemia in Rats: Modulation of the Hepatic Carbohydrate Response Element-Binding Protein-Mediated Pathway

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Huanqing Gao ◽  
Tao Guan ◽  
Chunli Li ◽  
Guowei Zuo ◽  
Johji Yamahara ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Liver ◽  
Binding Protein ◽  
Ppar Gamma ◽  
De Novo Lipogenesis ◽  
Nonesterified Fatty Acid ◽  
Alcoholic Extract ◽  
Response Element ◽  
Hepatic Expression ◽  
Element Binding Protein

Ginger has been demonstrated to improve lipid derangements. However, its underlying triglyceride-lowering mechanisms remain unclear. Fructose overconsumption is associated with increase in hepatic de novo lipogenesis, thereby resulting in lipid derangements. Here we found that coadministration of the alcoholic extract of ginger (50 mg/kg/day, oral gavage, once daily) over 5 weeks reversed liquid fructose-induced increase in plasma triglyceride and glucose concentrations and hepatic triglyceride content in rats. Plasma nonesterified fatty acid concentration was also decreased. Attenuation of the increased vacuolization and Oil Red O staining area was evident on histological examination of liver in ginger-treated rats. However, ginger treatment did not affect chow intake and body weight. Further, ginger treatment suppressed fructose-stimulated overexpression of carbohydrate response element-binding protein (ChREBP) at the mRNA and protein levels in the liver. Consequently, hepatic expression of the ChREBP-targeted lipogenic genes responsible for fatty acid biosynthesis was also downregulated. In contrast, expression of neither peroxisome proliferator-activated receptor- (PPAR-) alpha and its downstream genes, nor PPAR-gamma and sterol regulatory element-binding protein 1c was altered. Thus the present findings suggest that in rats, amelioration of fructose-induced fatty liver and hypertriglyceridemia by ginger treatment involves modulation of the hepatic ChREBP-mediated pathway.

scholarly journals The Role of the Carbohydrate Response Element-Binding Protein in Male Fructose-Fed Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (1) ◽  
pp. 36-44 ◽  
Author(s):  
Derek M. Erion ◽  
Violetta Popov ◽  
Jennifer J. Hsiao ◽  
Daniel Vatner ◽  
Kisha Mitchell ◽  
...  
Keyword(s):  
De Novo ◽  
Binding Protein ◽  
De Novo Lipogenesis ◽  
Sprague Dawley ◽  
Inherited Disorders ◽  
Response Element ◽  
Nonalcoholic Fatty Liver ◽  
Hepatic Expression ◽  
Triglyceride Secretion ◽  
Element Binding Protein

By 2030, nearly half of Americans will have nonalcoholic fatty liver disease. In part, this epidemic is fueled by the increasing consumption of caloric sweeteners coupled with an innate capacity to convert sugar into fat via hepatic de novo lipogenesis. In addition to serving as substrates, monosaccharides also increase the expression of key enzymes involved in de novo lipogenesis via the carbohydrate response element-binding protein (ChREBP). To determine whether ChREBP is a potential therapeutic target, we decreased hepatic expression of ChREBP with a specific antisense oligonucleotide (ASO) in male Sprague-Dawley rats fed either a high-fructose or high-fat diet. ChREBP ASO treatment decreased plasma triglyceride concentrations compared with control ASO treatment in both diet groups. The reduction was more pronounced in the fructose-fed group and attributed to decreased hepatic expression of ACC2, FAS, SCD1, and MTTP and a decrease in the rate of hepatic triglyceride secretion. This was associated with an increase in insulin-stimulated peripheral glucose uptake, as assessed by the hyperinsulinemic-euglycemic clamp. In contrast, ChREBP ASO did not alter hepatic lipid content or hepatic insulin sensitivity. Interestingly, fructose-fed rats treated with ChREBP ASO had increased plasma uric acid, alanine transaminase, and aspartate aminotransferase concentrations. This was associated with decreased expression of fructose aldolase and fructokinase, reminiscent of inherited disorders of fructose metabolism. In summary, these studies suggest that targeting ChREBP may prevent fructose-induced hypertriglyceridemia but without the improvements in hepatic steatosis and hepatic insulin responsiveness.

α-Terpineol induces fatty liver in mice mediated by the AMP-activated kinase and sterol response element binding protein pathway

2013 ◽  
Vol 55 ◽  
pp. 129-136 ◽  
Author(s):  
You-Jin Choi ◽  
Woo-Cheol Sim ◽  
Hyun Kyu Choi ◽  
Seung-Ho Lee ◽  
Byung-Hoon Lee
Keyword(s):  
Fatty Liver ◽  
Binding Protein ◽  
Response Element ◽  
Element Binding Protein

scholarly journals The Roles of Carbohydrate Response Element Binding Protein in the Relationship between Carbohydrate Intake and Diseases

2021 ◽  
Vol 22 (21) ◽  
pp. 12058
Author(s):  
Katsumi Iizuka
Keyword(s):  
Fatty Liver ◽  
Binding Protein ◽  
Carbohydrate Intake ◽  
Fibroblast Growth Factor 21 ◽  
High Fructose Corn Syrup ◽  
Response Element ◽  
Corn Syrup ◽  
High Fructose ◽  
Element Binding Protein ◽  
The Relationship

Carbohydrates are macronutrients that serve as energy sources. Many studies have shown that carbohydrate intake is nonlinearly associated with mortality. Moreover, high-fructose corn syrup (HFCS) consumption is positively associated with obesity, cardiovascular disease, and type 2 diabetes mellitus (T2DM). Accordingly, products with equal amounts of glucose and fructose have the worst effects on caloric intake, body weight gain, and glucose intolerance, suggesting that carbohydrate amount, kind, and form determine mortality. Understanding the role of carbohydrate response element binding protein (ChREBP) in glucose and lipid metabolism will be beneficial for elucidating the harmful effects of high-fructose corn syrup (HFCS), as this glucose-activated transcription factor regulates glycolytic and lipogenic gene expression. Glucose and fructose coordinately supply the metabolites necessary for ChREBP activation and de novo lipogenesis. Chrebp overexpression causes fatty liver and lower plasma glucose levels, and ChREBP deletion prevents obesity and fatty liver. Intestinal ChREBP regulates fructose absorption and catabolism, and adipose-specific Chrebp-knockout mice show insulin resistance. ChREBP also regulates the appetite for sweets by controlling fibroblast growth factor 21, which promotes energy expenditure. Thus, ChREBP partly mimics the effects of carbohydrate, especially HFCS. The relationship between carbohydrate intake and diseases partly resembles those between ChREBP activity and diseases.

scholarly journals Correction to: The role of hepatic transcription factor cAMP response element-binding protein (CREB) during the development of experimental nonalcoholic fatty liver: a biochemical and histomorphometric study

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ashraf K. Awaad ◽  
Maher A. Kamel ◽  
Magdy M. Mohamed ◽  
Madiha H. Helmy ◽  
Magda I. Youssef ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Fatty Liver ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Response Element ◽  
Nonalcoholic Fatty Liver ◽  
Histomorphometric Study ◽  
Element Binding Protein

An amendment to this paper has been published and can be accessed via the original article.

scholarly journals Identification of Liver X Receptor-Retinoid X Receptor as an Activator of the Sterol Regulatory Element-Binding Protein 1c Gene Promoter

2001 ◽  
Vol 21 (9) ◽  
pp. 2991-3000 ◽  
Author(s):  
Tomohiro Yoshikawa ◽  
Hitoshi Shimano ◽  
Michiyo Amemiya-Kudo ◽  
Naoya Yahagi ◽  
Alyssa H. Hasty ◽  
...  
Keyword(s):  
Retinoic Acid ◽  
Fatty Acid ◽  
Binding Protein ◽  
Regulatory Element ◽  
Gene Promoter ◽  
Liver X Receptor ◽  
Retinoid X Receptor ◽  
Response Element ◽  
Element Binding Protein ◽  
Sterol Regulatory Element

ABSTRACT In an attempt to identify transcription factors which activate sterol-regulatory element-binding protein 1c (SREBP-1c) transcription, we screened an expression cDNA library from adipose tissue of SREBP-1 knockout mice using a reporter gene containing the 2.6-kb mouse SREBP-1 gene promoter. We cloned and identified the oxysterol receptors liver X receptor (LXRα) and LXRβ as strong activators of the mouse SREBP-1c promoter. In the transfection studies, expression of either LXRα or -β activated the SREBP-1c promoter-luciferase gene in a dose-dependent manner. Deletion and mutation studies, as well as gel mobility shift assays, located an LXR response element complex consisting of two new LXR-binding motifs which showed high similarity to an LXR response element recently found in the ABC1 gene promoter, a reverse cholesterol transporter. Addition of an LXR ligand, 22(R)-hydroxycholesterol, increased the promoter activity. Coexpression of retinoid X receptor (RXR), a heterodimeric partner, and its ligand 9-cis-retinoic acid also synergistically activated the SREBP-1c promoter. In HepG2 cells, SREBP-1c mRNA and precursor protein levels were induced by treatment with 22(R)-hydroxycholesterol and 9-cis-retinoic acid, confirming that endogenous LXR-RXR activation can induce endogenous SREBP-1c expression. The activation of SREBP-1c by LXR is associated with a slight increase in nuclear SREBP-1c, resulting in activation of the gene for fatty acid synthase, one of its downstream genes, as measured by the luciferase assay. These data demonstrate that LXR-RXR can modify the expression of genes for lipogenic enzymes by regulating SREBP-1c expression, providing a novel link between fatty acid and cholesterol metabolism.

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