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)

Childhood obesity is a global epidemic and is associated with medical consequences. These consequences of childhood obesity include its association with cardiovascular risk factors, notably impaired glucose tolerance, hypertension, atherogenic dyslipidemia, micro inflammation, and comorbidities including nonalcoholic fatty liver disease (NAFLD), sleep apnoea, and early atherosclerosis. This article aims to demonstrate and review the local clinical evidences in Hong Kong Chinese children and adolescents in exploring the epidemiology and medical consequences associated with obesity in the youth population and highlighting the research direction in searching the etiology of these associations.
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PMID:Medical consequences of childhood obesity: a Hong Kong perspective. 2039 Dec 43

The objective of this study was to determine, in an adolescent population, the prevalence of nonalcoholic fatty liver disease (NAFLD) and the association of NAFLD and cardiovascular risk factors with carotid artery intima-media thickness (IMT), a marker of subclinical atherosclerosis. The authors conducted a population-based study among 642 randomly selected adolescents aged 11-13 years in Reggio Calabria, southern Italy, between November 2007 and October 2008. Prevalences of overweight and obesity were 30.5% and 13.5%, respectively. The overall prevalence of NAFLD was 12.5%, increasing to 23.0% in overweight/obese adolescents. In univariate analysis, increased IMT was positively associated with the presence of NAFLD, body mass index (BMI), waist circumference, systolic blood pressure (all P's < 0.001), diastolic blood pressure (P = 0.006), gamma-glutamyl transpeptidase (P = 0.006), alanine aminotransferase (P = 0.007), and C-reactive protein (P = 0.008) and was inversely associated with high density lipoprotein cholesterol (P < 0.001). In multivariate analysis, NAFLD (P = 0.002), BMI (P = 0.004), waist circumference (P = 0.003), and systolic blood pressure (P = 0.005) retained significant associations. The authors conclude that NAFLD, BMI, waist circumference, and systolic blood pressure are independent markers of increased IMT in a random sample of adolescents.
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PMID:Cardiovascular risk factors, nonalcoholic fatty liver disease, and carotid artery intima-media thickness in an adolescent population in southern Italy. 2045 71

Besides their well-established roles in dietary lipid absorption and cholesterol homeostasis, bile acids (BA) also act as metabolically active signaling molecules. The flux of reabsorbed BA undergoing enterohepatic circulation, arriving in the liver with the co-absorbed nutrients (e.g. glucose, lipids), provides a signal that coordinates hepatic triglyceride (TG), glucose and energy homeostasis. As signaling molecules with systemic endocrine functions, BA can activate protein kinases A and C as well as mitogen-activated protein kinase pathways. Additionally, they are ligands for a G-protein-coupled BA receptor (TGR5/Gpbar-1) and activate nuclear receptors such as farnesoid X receptor (FXR; NR1H4). FXR and its downstream targets play a key role in the control of hepatic de novo lipogenesis, very-low-density lipoprotein-TG export and plasma TG turnover. BA-activated FXR and signal transduction pathways are also involved in the regulation of hepatic gluconeogenesis, glycogen synthesis and insulin sensitivity. Via TGR5, BA are able to stimulate glucagon-like peptide-1 secretion in the small intestine and energy expenditure in brown adipose tissue and skeletal muscle. Dysregulation of BA transport and impaired BA receptor signaling may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Thus, BA transport and BA-controlled nuclear receptors and signaling pathways are promising drug targets for treatment of NAFLD. As such, FXR and/or TGR5 ligands have shown promising results in animal models of NAFLD and clinical pilot studies. Despite being a poor FXR and TGR5 ligand, ursodeoxycholic acid (UDCA) improves hepatic ER stress and insulin sensitivity. Notably, norUDCA, a side chain-shortened homologue of UDCA, improves fatty liver and atherosclerosis in Western diet-fed ApoE(-/-) mice. Collectively, these findings suggest that BA and targeting their receptor/signaling pathways may represent a promising approach to treat NAFLD and closely linked disorders such as obesity, diabetes, dyslipidemia and arteriosclerosis.
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PMID:Bile acids as regulators of hepatic lipid and glucose metabolism. 2046 Sep 15

Coenzyme A (CoA):diacylglycerol acyltransferase 1 (DGAT1) is 1 of the 2 known DGAT enzymes that catalyze the final and only committed step in triacylglycerol synthesis; this enzyme is considered to be a potential therapeutic target in metabolic disorders such as obesity and its related lipid abnormalities. Compound-Z, a novel specific small-molecule DGAT1 inhibitor, significantly reduced adipose tissue weight and tended to hepatic lipid accumulation in genetically obese KKAy mice. These actions were shown to almost the same extent in both a high-fat feeding condition in which triacylglycerols are synthesized mainly via exogenous fatty acid and a low-fat, high-carbohydrate feeding condition in which triacylglycerols are synthesized mainly via de novo fatty acid synthesis. This inhibitor also significantly reduced plasma and/or hepatic cholesterol levels in KKAy mice in a high-fat feeding condition. This cholesterol-lowering effect was suggested to be due to mainly decreases in cholesterol absorption from the small intestine. These results suggest that Compound-Z is a promising and attractive agent not only for the treatment of obesity but also hepatic steatosis and circulating lipid abnormalities that are the leading causes of atherosclerosis.
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PMID:Coenzyme A: diacylglycerol acyltransferase 1 inhibitor ameliorates obesity, liver steatosis, and lipid metabolism abnormality in KKAy mice fed high-fat or high-carbohydrate diets. 2047 3

Zebrafish are an increasingly popular vertebrate model organism in which to study biological phenomena. It has been widely used, especially in developmental biology and neurobiology, and many aspects of its development and physiology are similar to those of mammals. The popularity of zebrafish relies on its relatively low cost, rapid development and ease of genetic manipulation. Moreover, the optical transparency of the developing fish together with novel imaging techniques enable the direct visualization of complex phenomena at the level of the entire organism. This potential is now also being increasingly appreciated by the lipid research community. In the present review we summarize basic information on the lipid composition and distribution in zebrafish tissues, including lipoprotein metabolism, intestinal lipid absorption, the yolk lipids and their mobilization, as well as lipids in the nervous system. We also discuss studies in which zebrafish have been employed for the visualization of whole-body lipid distribution and trafficking. Finally, recent advances in using zebrafish as a model for lipid-related diseases, including atherosclerosis, obesity, diabetes and hepatic steatosis are highlighted. As the insights into zebrafish lipid metabolism increase, it is likely that zebrafish as a model organism will become an increasingly powerful tool in lipid research.
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PMID:Zebrafish: gaining popularity in lipid research. 2057 94

The global increase of children obesity has recently alerted top research teams. They have focused on finding causes present already in the prenatal period, on establishing diagnostic criteria for both childhood and adolescent ages, and on seeking for methods of monitoring risk and preventing metabolic syndrome manifestations. This paper is a literature review from prestigious medical journals that monitor the development of risks from the ontogenetic point of view. The paper deals not only with the issue of obesity itself, but also all risk complications like early atherosclerosis, higher blood pressure, insulin resistance, fatty liver, or sleep respiratory disorders.
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PMID:[Children in the risk of metabolic syndrome]. 2066 93

Several steps of the HDL-mediated reverse cholesterol transport (RCT) are transcriptionally regulated by the nuclear receptors LXRs in the macrophages, liver, and intestine. Systemic LXR activation via synthetic ligands induces RCT but also causes increased hepatic fatty acid synthesis and steatosis, limiting the potential therapeutic use of LXR agonists. During the last few years, the participation of the intestine in the control of RCT has appeared more evident. Here we show that while hepatic-specific LXR activation does not contribute to RCT, intestinal-specific LXR activation leads to decreased intestinal cholesterol absorption, improved lipoprotein profile, and increased RCT in vivo in the absence of hepatic steatosis. These events protect against atherosclerosis in the background of the LDLR-deficient mice. Our study fully characterizes the molecular and metabolic scenario that elects the intestine as a key player in the LXR-driven protective environment against cardiovascular disease.
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PMID:Intestinal specific LXR activation stimulates reverse cholesterol transport and protects from atherosclerosis. 2067 63

Serum gamma-glutamyl transferase (GGT) has been used as a marker of alcohol induced liver disease. Recent epidemiology and pathology studies have suggested its independent role in the pathogenesis and clinical evolution of cardiovascular diseases (CVD) promoting atherosclerosis through an oxidative process leading, within the atherosclerotic plaque, to LDL oxidation, metalloproteinase activation, cell proliferation and apoptosis. Besides it is known that GGT levels rise even in the normal range, with obesity and hepatic steatosis occurs, it is thought, which originates insulin resistance (IR). Being sure that IR is important in the development of type 2 diabetes and CVD, both very prevalent in Portugal, the authors considered as relevant to study the association of GGT with markers of multiple metabolic derangements: insulin-resistance (hyperinsulinemia, hyperglicemia, IR-HOMA = 3), obesity and dyslipidemia. So, a Portuguese sample population, consisted of 123 subjects (52 male and 71 female) was organized. As results were observed: elevation of GGT serum levels with the increasing risk of every marker and the same happened with metabolic syndrome and its components; compared with non obese the group of obese subjects exhibited elevated prevalence of risk factors, though in non obese subjects the percentages of insulin-resistance and dyslipidemias were high (hypercholesterolemia in both sexes, hypertriglyceridemia and low concentrations of HDL-c in men); association of serum GGT levels with every risk factor and metabolic syndrome. Though, as the association with the insulin-resistance state was particularly strong, it is thought that a high prevalence of non-alcoholic fatty liver disease (NAFLD) was present in the studied population. As serum determination of GGT activity is a low-cost, highly sensitive, accurate and frequently used laboratory test and there is association of this enzyme with the most important risk factors of diabetes type 2 and CVD, its serum levels should be considered as a marker of insulin-resistance when NAFLD is supposed to be present or there is obesity.
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PMID:[Association of gamma glutamyltransferase, metabolic syndrome and cardiovascular risk]. 2068 85

Growing evidence links the three mammalian lipin proteins, i.e., lipin-1, lipin-2 and lipin-3, to metabolic and cardiovascular diseases such as noninsulin-dependent diabetes mellitus and atherosclerosis. Lipin proteins play a dual function in lipid metabolism by acting as phosphatidate phosphatase (PAP) enzymes and as transcriptional regulators. Genetic variants within the human LPIN1 and LPIN2 genes are associated with metabolic syndromes. The fatty liver dystrophy (fld) mice carrying mutations within the Lpin1 gene display life-long deficiency in adipogenesis, insulin resistance, neonatal hepatosteatosis and hypertriglyceridemia, as well as increased atherosclerosis susceptibility. Cell culture studies show that hepatic lipin-1 expression is selectively stimulated by glucocorticoids and repressed by insulin, and its subcellular localization governs the assembly and secretion of very low density lipoproteins (VLDL). In noninsulin-dependent diabetes, glucocorticoid signals lead to dyslipidemia characterized by overproduction of VLDL and atherogenic remnants. This puts lipin-1 as a key integrator of hormonal signals to the liver in diabetic dyslipidemia. This review summarizes the current understanding of the role that hepatic lipin-1 plays in the synthesis, storage and compartmentalization of glycerolipids, and highlights the lipid metabolic consequences associated with dysregulated lipin expression.
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PMID:Lipin - The bridge between hepatic glycerolipid biosynthesis and lipoprotein metabolism. 2069 63

The unfolded protein response (UPR) was originally identified as a signaling network coordinating adaptive and apoptotic responses to accumulation of unfolded proteins in the endoplasmic reticulum (ER). More recent work has shown that UPR signaling can be triggered by a multitude of cellular events and that the UPR plays a critical role in the prevention, and also the progression, of a wide variety of diseases. Much attention has been paid to the role of the UPR in neurodegenerative diseases in the past. More recently, important roles for the UPR in diseases associated with the metabolic syndrome have been discovered. Here we review the role of the UPR in these diseases, including type 2 diabetes, atherosclerosis, fatty liver disease, and ischemia.
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PMID:Consequences of stress in the secretory pathway: The ER stress response and its role in the metabolic syndrome. 2070 Jul 4


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