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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The prevalence of fatty liver is rising in association with the global increase in obesity and type 2 diabetes. In the past, simple steatosis was regarded as benign, but the presence of another liver disease may provide a synergistic combination of steatosis, cellular adaptation, and oxidative damage that aggravates liver injury. In this review, a major focus is on the role of steatosis as a co-factor in chronic hepatitis C (HCV), where the mechanisms promoting fibrosis and the effect of weight reduction in minimizing liver injury have been most widely studied. Steatosis, obesity, and associated metabolic factors may also modulate the response to alcohol- and drug-induced liver disease and may be risk factors for the development of hepatocellular cancer. The pathogenesis of injury in obesity-related fatty liver disease involves a number of pathways, which are currently under investigation. Enhanced oxidative stress, increased susceptibility to apoptosis, and a dysregulated response to cellular injury have been implicated, and other components of the metabolic syndrome such as hyperinsulinemia and hyperglycemia are likely to have a role. Fibrosis also may be increased as a by-product of altered hepatocyte regeneration and activation of bipotential hepatic progenitor cells. In conclusion, active management of obesity and a reduction in steatosis may improve liver injury and decrease the progression of fibrosis.
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PMID:Steatosis: co-factor in other liver diseases. 1596 20

The number of obese and overweight Oklahomans and Americans has grown both steadily and rapidly in the last few decades. Along with this increase in weight, doctors now see a higher proportion of chronic, degenerative diseases such as cardiovascular disease, diabetes, cancer, and osteoarthritis. Poor diet, sedentary lifestyle, and poor stress and time management contribute to weight problems and illness. Lifestyle changes have no side effects or risks, other than the perceived challenge of implementing and maintaining them. Healthier habits offer multiple organ system benefits including weight control, less anxiety and depression, improved energy, better sleep, and lower rates of gastrointestinal problems, such as reflux, gallstones, and fatty liver. By providing accurate and comprehensible information, doctors can motivate and support patients to better safeguard their health and manage their weight. This article will suggest specific phrases to use in the framework of motivational interviewing, as discussed in the first article, Part I, in this 3-part series.
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PMID:Putting prevention into practice: counseling patients to prevent and decrease obesity. 1602 2

Chronic inflammatory processes produce an excess of ROS and DNA-reactive aldehydes from lipid peroxidation (LPO), such as trans-4-hydroxy-2-nonenal (HNE) and malondialdehyde (MDA), which can modify cellular macromolecules and drive to malignancy. Etheno-modified DNA bases are generated inter alia by reaction of DNA with the major LPO product, HNE. We are investigating steady-state levels of etheno-DNA adducts in organs with diseases related to persistent inflammatory processes that can lead to malignancies. We have developed ultrasensitive and specific methods for the detection of etheno-DNA base adducts in human tissues and in urine. Etheno-DNA adduct levels were found to be significantly elevated in the affected organs of subjects with chronic pancreatitis, ulcerative colitis and Crohn's disease. When patients with alcohol abuse-related hepatitis, fatty liver, fibrosis and cirrhosis were compared with asymptomatic livers, excess hepatic DNA damage was seen in the three latter patient groups. Etheno-deoxyadenosine excreted in urine was measured in HBV-infected patients diagnosed with chronic hepatitis, cirrhosis and hepatocellular carcinoma. As compared to controls, these patients had up to 90-fold increased urinary levels. Impaired or imbalanced DNA-repair pathways may influence the steady-state levels of etheno-DNA adducts in inflamed tissues. In conclusion, etheno-DNA adducts may serve as potential lead markers for assessing progression of inflammatory cancer-prone diseases. If so, the efficacy of human chemopreventive interventions for malignant disease prevention could be verified.
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PMID:Accumulation of lipid peroxidation-derived DNA lesions: potential lead markers for chemoprevention of inflammation-driven malignancies. 1609 77

Essential polyunsaturated fatty acids (PUFAs), linoleic acid n6 (LA) and linolenic acid (ALA) n3 obtained from the diet are precursors of the long-chain polyunsaturated fatty acids (Lc-PUFAs) arachidonic acid (AA) and docosahexaenoic acid (DHA) respectively. Consumption of PUFAs is related with a better neurological and cognitive development in newborns. It has been demonstrated that consumption of n-6 and n-3 PUFAs decreases blood triglycerides by increasing fatty acid oxidation through activation of PPARalpha or by reducing the activation of SREBP-1 inhibiting lipogenesis. Dietary PUFAs activate PPARalpha and PPARgamma increasing lipid oxidation, and decreasing insulin resistance leading in a reduction of hepatic steatosis. Beneficial effects of PUFAs have been observed in humans and in animals models of diabetes, obesity, cancer, and cardiovascular diseases. It is important to promote the consumption of PUFAs. Main food sources of PUFAs n-6 are corn, soy and safflower oil, and for PUFAs n-3 are fish, soy, canola oil and, flaxseed. Finally FAO/WHO recommends an optimal daily intake of n6/n3 of 5-10:1.
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PMID:[Molecular mechanisms of action and health benefits of polyunsaturated fatty acids]. 1618 7

This review highlights areas of clinical research in gastroenterology and hepatology that were published during the last year and were summarized during the most recent American Gastroenterological Association Plenary Session. The topics include a comparison of the risk of recurrent bleeding in patients taking clopidogrel versus aspirin plus a proton pump inhibitor, the introduction of rifaximin for the treatment of traveler's diarrhea, and the results of an oral vaccine for cholera tested in a high endemic area where there is also a high prevalence of human immunodeficiency virus infection. In inflammatory bowel disease, the impact of a biomarker of inflammation, C-reactive protein, to the response to a new biologic therapy is identified as potentially important because it might facilitate the selection of patients for these treatments. Results of device, endoscopic, and surgical treatment of obesity are reviewed, including the evidence of significant impact of surgery-induced weight loss on comorbid diseases. In the field of cancer, colonoscopic screening results in more polyps detected, down-staging of cancers identified, and improved cancer survival. A new familial syndrome associated with a serrated adenoma/carcinoma phenotype and variability in microsatellite instability is described. A controlled study demonstrates that a urine-derived substance, ulinastatin, reduces the risk of post-endoscopic retrograde cholangiopancreatography pancreatitis. Hepatic stellate cells are involved in the fibrogenesis associated with nonalcoholic fatty liver disease. These areas of clinical research demonstrate the breadth of significant advances that will impact on the clinical practice of gastroenterology and hepatology.
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PMID:GIH clinical research update: 2004-2005. 1636 Oct 39

The insulin resistance syndrome (IRS) is considered to be a new target of risk-reduction therapy. The IRS is a cluster of closely associated and interdependent abnormalities and clinical outcomes that occur more commonly in insulin-resistant/hyperinsulinemic individuals. This syndrome predisposes individuals to type 2 diabetes, cardiovascular diseases, essential hypertension, certain forms of cancer, polycystic ovary syndrome, nonalcoholic fatty liver disease, and sleep apnea. In patients at high risk for cardiovascular diseases, endothelial dysfunction is observed in morphologically intact vessels even before the onset of clinically manifest vascular disease. Indeed, there are several lines of evidence that indicate that endothelial function is compromised in situations where there is reduced sensitivity to endogenous insulin. It is well established that a decreased bioavailability of nitric oxide (NO) contributes to endothelial dysfunction. Furthermore, NO may modulate insulin sensitivity. Activation of NO synthase (NOS) augments blood flow to insulin-sensitive tissues (i.e. skeletal muscle, liver, adipose tissue), and its activity is impaired in insulin resistance. Inhibition of NOS reduces the microvascular delivery of nutrients and blunts insulin-stimulated glucose uptake in skeletal muscle. Furthermore, induction of hypertension by administration of the NOS inhibitor NG-monomethyl-L-arginine is also associated with insulin resistance in rats. Increased levels of asymmetric dimethylarginine (ADMA) are associated with endothelial vasodilator dysfunction and increased risk of cardiovascular diseases. An intriguing relationship exists between insulin resistance and ADMA. Plasma levels of ADMA are positively correlated with insulin resistance in nondiabetic, normotensive people. New basic research insights that provide possible mechanisms underlying the development of insulin resistance in the setting of impaired NO bioavailability will be discussed.
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PMID:Insulin resistance: potential role of the endogenous nitric oxide synthase inhibitor ADMA. 1644 67

Endogenously formed reactive oxygen species continuously damage cellular constituents including DNA. These challenges, coupled with exogenous exposure to agents that generate reactive oxygen species, are both associated with normal aging processes and linked to cardiovascular disease, cancer, cataract formation, and fatty liver disease. Although not all of these diseases have been definitively shown to originate from mutations in nuclear DNA or mitochondrial DNA, repair of oxidized, saturated, and ring-fragmented bases via the base excision repair pathway is known to be critical for maintaining genomic stability. One enzyme that initiates base excision repair of ring-fragmented purines and some saturated pyrimidines is NEIL1, a mammalian homolog to Escherichia coli endonuclease VIII. To investigate the organismal consequences of a deficiency in NEIL1, a knockout mouse model was created. In the absence of exogenous oxidative stress, neil1 knockout (neil1-/-) and heterozygotic (neil1+/-) mice develop severe obesity, dyslipidemia, and fatty liver disease and also have a tendency to develop hyperinsulinemia. In humans, this combination of clinical manifestations, including hypertension, is known as the metabolic syndrome and is estimated to affect >40 million people in the United States. Additionally, mitochondrial DNA from neil1-/- mice show increased levels of steady-state DNA damage and deletions relative to wild-type controls. These data suggest an important role for NEIL1 in the prevention of the diseases associated with the metabolic syndrome.
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PMID:The metabolic syndrome resulting from a knockout of the NEIL1 DNA glycosylase. 1644 48

We studied the expression levels of fatty acid binding proteins in breast normal and cancer cell lines. Liver fatty acid binding protein (L-FABP) and intestine fatty acid binding proteins were shown to be up-regulated in breast cancer cell lines while adipose- and epidermal-fatty acid binding proteins were down regulated in breast cancer cells compared to normal breast cell lines. We have previously shown that blocking the expression of L-FABP resulted in remarkable effects on apoptosis and cell proliferation of prostate cancer cell lines (Hammamieh et al 2004). To study the mechanism of effect of the liver fatty acid binding protein in breast cancer cells, we designed an antisense oligodeoxynucleotide to block the production of liver-FABP in MCF-7 cells. The antisense was shown to inhibit the expression of L-FABP and to induce apoptosis in MCF-7 cells. This study examines the mechanism by which L-FABP antisense regulates proliferation and apoptosis in breast cancer cell lines. We used human cDNA microarrays to explore differentially expressed genes in MCF-7 breast cancer cells treated with L-FABP antisense oligonucleotide. Some of the genes that were differentially expressed were confirmed using quantitative RT-PCR. Genes related to cell growth, proliferation and angiogenesis showed significant variations. This suggests a possible use of these antisense ODNs as therapeutic agents for breast cancer in future.
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PMID:Expression patterns of fatty acid binding proteins in breast cancer cells. 1647 Oct 39

Insulin-mediated glucose disposal varies widely in apparently healthy human beings, and the more insulin resistant an individual, the more insulin they must secrete in order to prevent the development of type 2 diabetes. However, the combination of insulin resistance and compensatory hyperinsulinemia increases the likelihood that an individual will be hypertensive, and have a dyslipidemia characterized by a high plasma triglyceride (TG) and low high-density lipoprotein cholesterol (HDL-C) concentration. These changes increase risk of cardiovascular disease (CVD), and in 1988, this cluster of related abnormalities was designated as comprising a syndrome (X). Several other clinical syndromes are now known to be associated with insulin resistance and compensatory hyperinsulinemia. For example, polycystic ovary syndrome appears to be secondary to insulin resistance and compensatory hyperinsulinemia. More recently, studies have shown that the prevalence of insulin resistance/hyperinsulinemia is increased in patients with nonalcoholic fatty liver disease, and there are reports that certain forms of cancer are more likely to occur in insulin resistant/hyperinsulinemic persons. Finally, there is substantial evidence of an association between insulin resistance/hyperinsulinemia, and sleep disordered breathing. Given the rapid increase in the number of clinical syndromes and abnormalities associated with insulin resistance/hyperinsulinemia, it seems reasonable to suggest that the cluster of these changes related to the defect in insulin action be subsumed under the term of the insulin resistance syndrome. In addition to the identification of additional clinical syndromes related to insulin resistance/hyperinsulinemia, a number of new risk factors have been recognized that would increase CVD risk in these individuals. Thus, in addition to a high TG and a low HDL-C, the atherogenic lipoprotein profile in insulin resistant/hyperinsulinemic individuals also includes the appearance of smaller and denser low density lipoprotein particles, and the enhanced postprandial accumulation of remnant lipoproteins; changes identified as increasing risk of CVD. Elevated plasma concentrations of plasminogen activator inhibitor-1 (PAI-1) have been shown to be associated with increased CVD, and there is evidence of a significant relationship between PAI-1 and fibrinogen levels and both insulin resistance and hyperinsulinemia. Evidence is also accumulating that sympathetic nervous system (SNS) activity is increased in insulin resistant, hyperinsulinemic individuals, and, along with the salt sensitivity associated with insulin resistance/hyperinsulinemia, increases the likelihood that these individuals will develop essential hypertension. The first step in the process of atherogenesis is the binding of mononuclear cells to the endothelium, and mononuclear cells isolated from insulin resistant/hyperinsulinemic individuals adhere with greater avidity. This process is modulated by adhesion molecules produced by endothelial cells, and there is a significant relationship between degree of insulin resistance and the plasma concentration of the several of these adhesion molecules. Further evidence of the relationship between insulin resistance and endothelial dysfunction is the finding that asymmetric dimethylarginine, an endogenous inhibitor of the enzyme nitric oxide synthase, is increased in insulin resistant/hyperinsulinemic individuals. Finally, plasma concentrations of several inflammatory markers are elevated in insulin resistant subjects. It is obvious that the cluster of abnormalities associated with insulin resistance and compensatory hyperinsulinemia contains many well-recognized CVD risk factors, choosing which one, or ones, that are primarily responsible for the accelerated atherogenesis that characterizes this syndrome is not a simple task. Indeed, efforts to try to do so by the use of multiple regression analysis of epidemiological data may be more misleading than helpful.
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PMID:Insulin resistance, the insulin resistance syndrome, and cardiovascular disease. 1648 19

The fatty liver Shionogi (FLS) mouse is a new inbred strain that spontaneously develops fatty liver with infiltration of mononuclear cells. Moreover, this mouse is known to frequently develop spontaneous hepatic cancers. Recently, human non-alcholic steatohepatitis (NASH) has been focused of attention regarding hepatocellular carcinoma. Therefore, this mouse has potential as a model for human hepatic cancer due to steatosis. It is of interest therefore, whether it exhibits elevated susceptibility not only regarding spontaneous tumor development but also to chemical hepatocarcinogens. To examine this concern, we examined diethylnitrosamine (DEN) hepatocarcinogenesis in FLS mice with 30ppm in drinking water for 26 weeks in comparison to two other strains of mice, C3H and C57. The induction of spontaneous and DEN-induced hepatic tumors was clearly increased in the FLS case, along with levels of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, as compared to the other strains, with or without DEN treatment. These results indicate that the oxidative DNA stress is intimately involved in hepatocarcinogenesis in FLS mice and provide further support for use of this mouse as a useful model for investigating hepatocarcinogenesis due to human hepatic steatosis.
Cancer Lett 2007 Feb 08
PMID:High sensitivity of fatty liver Shionogi (FLS) mice to diethylnitrosamine hepatocarcinogenesis: comparison to C3H and C57 mice. 1656 78


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