Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of present study was to identify the visceral adipose tissue genes differentially expressed in a well-characterized rat model of high-fat diet (HFD)-induced obesity. Male Sprague-Dawley rats were fed either the HFD (17 g lard + 3 g corn oil/100 g) or the normal diet (5 g corn oil/100 g) for 9 weeks. The HFD rats weighed 55% more and accumulated 85% to 133% greater visceral fats than did the normal-diet rats (P < .05). Animals given the HFD for 9 weeks acquired dyslipidemia, fatty liver, insulin resistance, and hyperleptinemia along with the overexpression of several obesity-related genes, such as leptin, tumor necrosis factor alpha, resistin, peroxisome proliferator-activated receptor gamma2, CCAAT/enhancer-binding protein alpha, and sterol regulatory element-binding protein-1c, in the epididymal adipose tissue. The differential gene expression profile obtained from the cDNA microarray analysis followed by the real-time polymerase chain reaction confirmation led to a recruitment of several uncharacterized adipose tissue genes responding to the HFD. We report herein, for the first time, that a series of genes which might be implicated in the insulin-stimulated glucose transporter 4 translocation, such as protein phosphatase 2 (formerly 2A), cell division cycle 42-interacting protein 4, syntaxin 6, linker of T-cell receptor pathways 10, as well as the genes which might be involved in cancer development, such as heat shock 10-kd protein 1, and ras-related C3 botulinum toxin substrate 1, were differentially expressed in the epididymal adipose tissue of rats rendered obese by an HFD.
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PMID:Genes are differentially expressed in the epididymal fat of rats rendered obese by a high-fat diet. 1908 40

The epidemiology of hepatocellular cancer (HCC) can be viewed from several important perspectives. The conventional perspective includes the overall public health impact of HCC, which is increasing in incidence in many regions of the world. The epidemiology of HCC can also be viewed from the perspective of variation in underlying disease associations such as viral hepatitis or the recently recognized link to nonalcoholic fatty liver disease (NAFLD). Of perhaps increasing importance with recent advances in therapy of HCC, the epidemiology of HCC can also be viewed from the perspective of variation in HCC biology. This lesser known perspective may depend in part on the underlying liver disease and the cell origin of the cancer, whether of hepatocyte or stem cell origin. This aspect is likely to become central to diagnosis and management of HCC with the further development of targeted therapeutics. The relative efficacy of these agents will likely depend on the biochemical pathways active in a given hepatocellular malignancy. This, in turn, is likely to be related to the epidemiological associations of HCC.
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PMID:The epidemiology of hepatocellular cancer: from the perspectives of public health problem to tumor biology. 1914 1

Several lines of evidence have suggested that oxidative stress plays an important role for the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, by using immunohistochemical staining of liver biopsy samples, we measured hepatic 7,8-dihydro-8-oxo-2' deoxyguanosine (8-oxodG), a DNA base-modified product generated by hydroxyl radicals, of 38 NASH patients and compared with 24 simple steatosis and 10 healthy subjects. Relation of hepatic 8-oxodG with clinical, biochemical, and histologic variables and changes after iron reduction therapy (phlebotomy plus iron-restricted diet) were also examined. Hepatic 8-oxodG levels were significantly higher in NASH compared with simple steatosis (17.5 versus 2.0 8-oxodG-positive cells/10(5) microm(2); P < 0.0001). 8-oxodG was significantly related to iron overload condition, glucose-insulin metabolic abnormality, and severities of hepatic steatosis in NASH patients. Logistic regression analysis also showed that hepatic iron deposit and insulin resistance were independent variables associated with elevated hepatic 8-oxodG. After the iron reduction therapy, hepatic 8-oxodG levels were significantly decreased (from 20.7 to 13.8 positive cells/10(5) microm(2); P < 0.01) with concomitant reductions of serum transaminase levels in NASH patients. In conclusion, iron overload may play an important role in the pathogenesis of NASH by generating oxidative DNA damage and iron reduction therapy may reduce hepatocellular carcinoma incidence in patients with NASH.
Cancer Epidemiol Biomarkers Prev 2009 Feb
PMID:Iron overload is associated with hepatic oxidative damage to DNA in nonalcoholic steatohepatitis. 1919 Jan 44

[1-(13)C]pyruvate is a readily polarizable substrate that has been the subject of numerous magnetic resonance spectroscopy (MRS) studies of in vivo metabolism. In this work (13)C-MRS of hyperpolarized [1-(13)C]pyruvate was used to interrogate a metabolic pathway involved in neither aerobic nor anaerobic metabolism. In particular, ethanol consumption leads to altered liver metabolism, which when excessive is associated with adverse medical conditions including fatty liver disease, hepatitis, cirrhosis, and cancer. Here we present a method for noninvasively monitoring this important process in vivo. Following the bolus injection of hyperpolarized [1-(13)C]pyruvate, we demonstrate a significantly increased rat liver lactate production rate with the coadministration of ethanol (P = 0.0016 unpaired t-test). The affect is attributable to increased liver nicotinamide adenine dinucleotide (NADH) associated with ethanol metabolism in combination with NADH's role as a coenzyme in pyruvate-to-lactate conversion. Beyond studies of liver metabolism, this novel in vivo assay of changes in NADH levels makes hyperpolarized [1-(13)C]pyruvate a potentially viable substrate for studying the multiple in vivo metabolic pathways that use NADH (or NAD(+)) as a coenzyme, thus broadening the range of applications that have been discussed in the literature to date.
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PMID:In vivo measurement of ethanol metabolism in the rat liver using magnetic resonance spectroscopy of hyperpolarized [1-13C]pyruvate. 1952 98

One of the most important chaperones located on endoplasmic reticulum, GRP78, referred as BiP (immunoglobulin heavy chain binding protein), belongs to heat shock protein 70 family. GRP78 exists conservatively among a wide variety of biological species, and acts as a central regulator of endoplasmic reticulum (ER) functions, participating in ER protein folding and assembly process, and maintaining ER Ca2+ homeostasis, unfolded protein response and specific anti-apoptotic actions. Specific regulatory cis-elements such as ER stress response element (ERSE) and cAMP response element (CRE) were identified on the promoter of GRP78. Dynamic epigenetic interactions between specific transcription factors such as AFT6 and regulatory elements in GRP78 gene promoter might contribute to human GRP78 constitutive or inducible transcription, resulting from some physiological and pathological stresses. Recently, cellular relationship between GRP78 expression and hepatic steatosis, cancer and nervous system diseases in human was underwent further clinical and biochemical research, which will benefit to human beings.
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PMID:[Glucose regulated protein 78 kD]. 1955 42

Comprehensive studies support the notion that oltipraz [4-methyl-5-(2-pyrazynyl)-1,2-dithiole-3-thione] and its congeners exert cancer chemopreventive effects by the prevention, inhibition or reversal of carcinogenic processes. Recently, it was found that dithiolethione compounds had the activities to prevent or treat fibrosis, insulin resistance, and mitochondrial protective effects in the liver by a mechanism involving AMP-activated protein kinase (AMPK) and/or 70-kDa ribosomal protein S6 kinase 1 (S6K1). Moreover, chemical regulation of the AMPK-S6K1 pathway was found to affect Liver X receptor (LXR) activity and lipogenesis, leading to the identification of AMPK and S6K1 as targets for treating hepatic steatosis. These biological activities of dithiolethiones may offer a novel approach to pharmaceutical intervention. This review focuses on the interaction between oltipraz and the AMPK-mTOR-S6K1 pathway, which regulates genes that confer hepatocyte protection from intoxication, disrupted energy metabolism, and inflammation. In terms of therapeutic potential, the findings reviewed here demonstrate a new therapeutic potential for dithiolethiones, which function in a unique manner, and offer the possibility of new treatments for hepatic diseases.
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PMID:Therapeutic potential of dithiolethiones for hepatic diseases. 1956 26

Nonalcoholic steatohepatitis (NASH), one of the NAFLDs (nonalcoholic fatty liver diseases), is regarded as a hepatic manifestation of metabolic syndrome. NASH can progress to cirrhosis, and possibly to hepatic malignancy. Currently, liver biopsy is the only reliable method of assessing the presence or absence of NASH and the stage of fibrosis. The finding of steatosis with evidence of hepatocyte injury such as inflammation, ballooning, degeneration, and/or fibrosis, is generally essential for making a diagnosis of NASH. However, its diagnostic criteria have not yet been established. The pathologic findings of NASH and related diseases, and the grading system currently in use are reviewed herein.
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PMID:[Pathology of nonalcoholic steatohepatitis]. 1958 64

Allopurinol is an inhibitor of xanthine oxidoreductase (XOR) and inhibits the generation of uric acid (UA) as the final product of purine catabolism, as well as the resulting generation of superoxide (O2(-)), in humans. Elevation of the serum UA (SUA) level, referred to as hyperuricemia (HU), eventually leads to gout and allopurinol has been used for the treatment of HU and gout. Studies have revealed the role of elevated SUA levels and the associated oxidative stress (OS) in a broad spectrum of pathological conditions and it is anticipated that these findings would also expand the use of allopurinol as a therapeutic drug. This article presents a review of reports, mainly of recent studies, on the efficacy of allopurinol in various diseases and explores novel potential uses of the drug. Important novel and potential uses of great interest include metabolic syndrome (MetS) and related disorders, chronic kidney disease (CKD), nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH). Ischemia-reperfusion injury and mucositis, encountered as adverse effects of cancer treatment, have also been under investigation as potential targets for allopurinol.
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PMID:Allopurinol, an inhibitor of uric acid synthesis--can it be used for the treatment of metabolic syndrome and related disorders? 1958 65

Primary liver cancer is the fifth most common malignancy worldwide and the third leading cause of cancer mortality. Non-alcoholic fatty liver disease is the most common cause of chronic liver disease in the United States encompassing a spectrum of entities marked by hepatic steatosis in the absence of significant alcohol consumption. Although simple steatosis follows a generally benign course, the more aggressive form, non-alcoholic steatohepatitis, can progress to cirrhosis and result in complications including hepatocellular carcinoma. A significant number of cases of hepatocellular carcinoma remain cryptogenic without known underlying chronic liver disease. It is increasingly recognized that non-alcoholic steatohepatitis likely accounts for a substantial portion of cryptogenic hepatocellular carcinoma.
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PMID:NASH and HCC. 1981 10

Hepatocellular carcinoma (HCC) is the most rapidly increasing cause of cancer death in the United States. Although many risk factors for HCC are well defined, including hepatitis B virus (HBV), hepatitis C virus (HCV), and alcohol, most series have indicated that 5% to 30% of patients with HCC lack a readily identifiable risk factor for their cancer. The majority of "cryptogenic" HCC in the United States is attributed to nonalcoholic fatty liver disease (NAFLD), a hepatic manifestation of the metabolic syndrome. The metabolic syndrome is a constellation of problems that includes insulin resistance, obesity, hypertension, and hyperlipidemia. Increasingly, components of the metabolic syndrome are being linked to various forms of cancer with respect to both increased risk of disease and worsened outcome. In this review, the authors focused on the relation between metabolic syndrome and HCC. They investigated the increased risks of HCC among individuals with features of metabolic syndrome, potentially worsened cancer outcomes in these patients, possible pathogenic mechanisms to explain these relations, and treatment options for those with NAFLD and its progressive counterpart, nonalcoholic steatohepatitis. It is predicted that metabolic syndrome will lead to large increases in the incidence of HCC over the next decades. A better understanding of the relation between these 2 diseases ultimately should lead to improved screening and treatment options for patients with HCC.
Cancer 2009 Dec 15
PMID:Metabolic syndrome and hepatocellular carcinoma: two growing epidemics with a potential link. 1983 57


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