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 recent technological advances in high-throughput gene expression analysis allow the simultaneous investigation of thousands of genes. These technologies represent promising tools for the identification of new drug targets and considerable progress has been achieved in cancer research where microarray data provide a basis to design new drugs and to predict adverse reactions and the efficacy of chemotherapy. The metabolic syndrome represents a cluster of disorders including high blood pressure, insulin resistance/type 2 diabetes mellitus, visceral obesity and dyslipidaemia with fatty liver disease being a common associated complication. High-throughput gene expression analyses using GeneChips, microarrays and serial analysis of gene expression (SAGE) have been applied to study global gene expression in insulin resistance/type 2 diabetes mellitus. Type 2 diabetes mellitus is a multifactorial and polygenic disease by which several organs are affected. Therefore, the identification of both, disease causing and therapeutically relevant target genes is an ambitious challenge. In the present review we focus on genomic approaches that used biopsies from human skeletal muscle, liver and adipose tissue, the main organs affected by insulin resistance. Members of the PPARgamma coactivator-1 (PGC-1) family of transcriptional coactivators are decreased in skeletal muscle in insulin resistance accounting for the reduced expression of genes involved in mitochondrial oxidative phosphorylation. Hepatic steatosis is also linked to alterations in mitochondrial phosphorylation and oxidative metabolism. An up regulation of pro-inflammatory genes can be detected in early stages of fatty liver disease without histological signs of inflammation. Impaired adipogenesis, intra-adipose accumulation of macrophages and a sustained release of inflammatory and acute phase proteins are characteristic features of adipose tissue in obesity and may aggravate systemic insulin resistance.
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PMID:Does global gene expression analysis in type 2 diabetes provide an opportunity to identify highly promising drug targets? 1822 Sep 45

Nonalcoholic fatty liver disease (NAFLD) is a group of diseases with excess fat in liver in the absence of a poorly defined limit of alcohol consumption. Most common variety, a universal public health problem, is associated with insulin resistance caused by a host of genetic and epigenetic defects modulated by life style and environmental factors. In fact the term NAFLD is loose to incorporate so many etiologies except alcoholism and few other etiologies, presenting as fat in liver. However as a sign fatty liver is very important in predicting the risk of diabetes, cardiovascular disease, stroke, cirrhosis and cancer. Abnormal fat accumulation can result from several defects in nuclear receptors associated with lipid sensing, synthesis and oxidation like LXR, FXR, SREBP, ChREBP and PPAR; defects in the lipid influx-efflux channels, insulin signaling, proteins involved in fatty acid catabolism, defects in adipose tissue development and function, inappropriate nutrition and finally defects in neural regulatory mechanisms. The progress of the disease is determined by the basic defects which results in fat accumulation, an individual's immunological response to the accumulated fat and its derivatives and the oxidant stress response. Congregation of unrelated genetic defects under same diagnosis 'NAFLD' can result in inefficient patient management. Further studies are required to understand the molecular basis of fatty liver to enable a personalized management of diseases presenting as fatty liver in the absence of alcohol abuse.
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PMID:The blind men 'see' the elephant-the many faces of fatty liver disease. 1824 Mar 40

An 11-year-old male developed systemic calciphylaxis during induction therapy for acute lymphoblastic leukemia. His predisposing conditions were hypercalcemia, supplements for pamidronate-induced hypocalcemia and hypophosphatemia and renal insufficiency. He died of cardiorespiratory arrest on the 20th day of induction treatment. Autopsy revealed extensive calcium deposits in the heart, lungs and kidneys. He had diffused alveolar damage, acute tubular necrosis, chronic pancreatitis and marked hepatic steatosis. Systemic calcium deposition may progress rapidly in children with hypercalcemia of malignancy. Since pamidronate reduces mineral resorption from tissues, calcium and phosphate replacements increase systemic mineral deposits. Thus, mineral supplements should be considered only to combat symptoms.
Pediatr Blood Cancer 2008 Oct
PMID:Systemic calciphylaxis. 1849 73

Obesity is known to be a major aetiological factor in the development of hypertension. It also leads to dyslipidaemia and raised blood glucose. All of these are components of the metabolic syndrome. Thus, hypertension, as part of the syndrome, is often found together with these other abnormalities. Obesity raises blood pressure by a number of mechanisms, including activation of the sympathetic nervous system and the renin- angiotensin system. Apart from cardiovascular disease and diabetes, the metabolic syndrome is also associated with fatty liver disease, sleep apnoea and some malignancies. Measures to reduce obesity through lifestyle changes are therefore highly desirable, not because of reductions in blood pressure alone.
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PMID:Hypertension as part of the metabolic syndrome. 1854 89

Potential causes of abnormal liver function tests include viral hepatitis, alcohol intake, nonalcoholic fatty liver disease, autoimmune liver diseases, hereditary diseases, hepatobiliary malignancies or infection, gallstones and drug-induced liver injury. Moreover, the liver may be involved in systemic diseases that mainly affect other organs. Therefore, in patients without etiology of liver injury by screening serology and diagnostic imaging, but who have systemic diseases, the abnormal liver function test results might be caused by the systemic disease. In most of these patients, the systemic disease should be treated primarily. However, some patients with systemic disease and severe liver injury or fulminant hepatic failure require intensive treatments of the liver.
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PMID:Liver in systemic disease. 1863 53

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.
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PMID:Hepatocellular carcinoma: epidemiology, risk factors and pathogenesis. 1866 17

Group VI phospholipase A2 (PLA2) is a family of acyl hydrolases that targets the sn-2 fatty acid on the glycerophospholipid (GPL) backbone. These enzymes are grouped together based on structural homologies and catalytic activities that are independent of calcium and hence are also called the iPLA(2)s. Although the best characterized of these enzymes, iPLA2beta and iPLA2gamma, have long been proposed as homeostatic enzymes involved in basal GPL metabolism, recent studies indicate roles for these enzymes in biomedically relevant processes as well. For example, iPLA2 modulates calcium homeostasis by promoting replenishment of intracellular calcium stores. This function is likely of importance in the pathogenesis of Duchenne muscular dystrophy and potentially allergy as well. iPLA2 has a variety of roles in bacterial pathogenesis and the host response against bacterial and fungal infections. These characteristics suggest that the enzyme as a potential target to control infectious diseases. iPLA2 is linked to both proliferation and chemotherapy-induced apoptosis of tumor cells. As such, the enzyme is a potential target for cancer chemotherapy. Recent studies indicate essential roles for iPLA2 in glucose homeostasis, maintenance of energy balance, adipocyte development, and hepatic lipogenesis. Thus, the enzyme is an attractive target for drugs to control type II diabetes, fatty liver disease, and other manifestations of the metabolic syndrome. Several recent studies have associated iPLA2 inactivation with neurodegenerative diseases, suggesting the possibility that products of the iPLA2 reaction as potential treatments for these disorders. Together, these observations suggest iPLA2 as a novel and important target for drug development. However given the ubiquitous expression of the enzyme and its roles in basal GPL metabolism, drug strategies targeting iPLA2 must exhibit exquisite selectivity to avoid undesired side effects. Furthermore, the cell-specific nature of many iPLA2 functions may present another challenge in the design and implementation of drugs targeted to the enzyme.
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PMID:Group VI phospholipases A2: homeostatic phospholipases with significant potential as targets for novel therapeutics. 1869 Oct 15

Multinodular fatty liver (MNFL) is a pattern of fatty infiltration of the liver characterized by multiple well-circumscribed nodules on hepatic imaging, often raising the concern of metastatic malignancy. Here we describe a case of MNFL and review the published literature. There is likely some association between traditional risk factors for hepatic steatosis (e.g. alcohol, rapid weight change, metabolic syndrome, medications, TPN) and MNFL. Further study and reporting of cases of MNFL are needed to better characterize its pathogenesis and natural history.
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PMID:Multinodular fatty liver after herpes-zoster vaccine: case report and review of the literature. 1903 41

Fatty liver disease is a problem of growing clinical importance due to its association with the increasingly prevalent conditions of obesity and diabetes. While steatosis represents a reversible state of excess intrahepatic lipid, it is also associated with increased susceptibility to oxidative and cytokine stresses and progression to irreversible hepatic injury characterized by steatohepatitis, cirrhosis, and malignancy. Currently, the molecular mechanisms underlying progression of this dynamic disease remain poorly understood, particularly at the level of transcriptional regulation. We recently constructed a library of stable monoclonal green fluorescent protein (GFP) reporter cells that enable transcriptional regulation to be studied dynamically in living cells. Here, we adapt the reporter cells to create a model of steatosis that will allow investigation of transcriptional dynamics associated with the development of steatosis and the response to subsequent "second hit" stresses. The reporter model recapitulates many cellular features of the human disease, including fatty acid uptake, intracellular triglyceride accumulation, increased reactive oxygen species accumulation, decreased mitochondrial membrane potential, increased susceptibility to apoptotic cytokine stresses, and decreased proliferation. Finally, to demonstrate the utility of the reporter cells for studying transcriptional regulation, we compared the transcriptional dynamics of nuclear factor kappaB (NFkappaB), heat shock response element (HSE), and glucocorticoid response element (GRE) in response to their classical inducers under lean and fatty conditions and found that intracellular lipid accumulation was associated with dose-dependent impairment of NFkappaB and HSE but not GRE activation. Thus, steatotic reporter cells represent an efficient model for studying transcriptional responses and have the potential to provide important insights into the progression of fatty liver disease.
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PMID:Development of an in vitro cell culture model of hepatic steatosis using hepatocyte-derived reporter cells. 1906 Dec 38

Endoplasmic reticulum (ER) stress and activation of the unfolded protein response have been linked to many human disorders, including obesity, type 2 diabetes, and cancer. In this issue of Developmental Cell,Rutkowski et al. (2008) show that unresolved ER stress contributes to metabolic dysfunction and hepatic steatosis.
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PMID:ER stress and lipogenesis: a slippery slope toward hepatic steatosis. 1908 Oct 72


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