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 prevalence of non-alcoholic fatty liver disease (NAFLD) ranges from 17% to 33% in the general population. It is frequently associated with obesity (60-90%), dyslipidemia (27-92%), diabetes (28-55%) and arterial hypertension (22%); in the presence of the metabolic syndrome, its incidence is 2-fold higher. NAFLD can be considered as an early mediator of the atherosclerotic process with which it shares some pathogenetic mechanisms (insulin resistance, oxidative stress, endothelial dysfunction, inflammatory activation). Patients with NAFLD are usually asymptomatic, high values of liver enzyme tests being the most common finding. Although liver biopsy is the current gold standard for diagnosis of NAFLD, it is not a practical screening tool given the cost, time-consuming nature and potential morbidity of this procedure. Ultrasound is a relatively inexpensive technique of liver imaging. Patients with NAFLD exhibit a higher mortality rate than the general population. The most frequent causes of death are represented by liver-related diseases, malignant neoplasms and cardiovascular disease, the latter being as frequent as malignant neoplasms. Data on cardiac abnormalities in patients with NAFLD are scarce. Abnormalities in left ventricular geometry and diastolic function have been described in patients with NAFLD as well as a more severe coronary artery disease characterized by vulnerable plaques, though observed in small cohort studies. According to the available evidence, NAFLD should be taken into consideration by cardiologists because its identification allows a better risk stratification in both primary and secondary prevention. Its correlation with coronary artery disease strongly suggests that NAFLD plays a proatherogenic role per se, in addition to the well known atherosclerotic risk factors. The finding of increased fatty liver content should prompt to assess the coexistence of other risk factors as well as to tailor the appropriate therapeutic regimen in order to reduce fatty liver content.
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PMID:[Non-alcoholic fatty liver disease: a new challenge for cardiologists]. 2134 25

Statins play an important role in the care of patients with cardiovascular disease and have a good safety record in clinical practice. The risk of hepatic injury caused by statins is estimated to be about 1 percent, similar to that of patients taking a placebo. Patients with transaminase levels no more than three times the upper limit of normal can continue taking statins; often the elevations will resolve spontaneously. Coexisting elevations of transaminase levels from nonalcoholic fatty liver disease and stable hepatitis B and C viral infections are not contra- indications to statin use. Although myalgias are common with statin use, myositis and rhabdomyolysis are rare. When prescribed at one-half the recommended maximal dosage or less, statins are associated with an incidence of myopathy similar to that of placebo; therefore, rou- tine monitoring of creatine kinase levels in asymptomatic patients is not recommended. Myopathic symptoms usually resolve approximately two months after discontinuing the statin, and the same statin can be restarted at a lower dosage, or patients can try a different statin. Clinically important drugs that interact with statins and increase the risk of adverse effects include fibrates, diltiazem, verapamil, and amiodarone.
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PMID:Considerations for safe use of statins: liver enzyme abnormalities and muscle toxicity. 2140 82

Obesity is a worldwide epidemic with multiple obesity-associated health problems including type 2 diabetes, hypertension, and cardiovascular disease. Adipose tissue serves as a fuel storage depot, but also plays a pivotal role in homeostasis of energy expenditure, appetite regulation, glucose regulation, and immunity. Both genetics and environment play important roles in adipose tissue function and dysfunction. Obesity represents an abnormal accumulation of adipose tissue resulting from chronic overnutrition and reduced physical activity. The nature of this increased accumulation of fat tissue, whether hyperplasia or hypertrophy, local or ectopic, is associated with deleterious perturbations including excess fatty acid secretion, increased production of inflammatory cytokines, and abnormal adipocyte hormone signaling resulting in insulin resistance. In the setting of obesity, insulin resistance and chronic inflammation is postulated to play a role in development of type 2 diabetes and other obesity-related comorbidities including obstructive sleep apnea, hepatic steatosis, polycystic ovarian syndrome, hypertension and cardiovascular disease. Although the exact mechanism of these relationships are complex and not completely understood, the ability to store and limit fatty acid deposition to adipose tissue is a common component to remaining insulin sensitive, controlling the inflammatory cascade and reducing the risk of developing obesity-related comorbidities.
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PMID:Obesity and the development of type 2 diabetes: the effects of fatty tissue inflammation. 2143 93

Hepatic steatosis, considered the first step in the pathophysiologic continuum of non-alcoholic fatty liver disease, is estimated to afflict 30% of the US population and over 75% of patients with Type 2 diabetes. Given the expected rise in the prevalence of obesity and Type 2 diabetes in the following decades, hepatic steatosis will, if not already, become an epidemic. The consequences of hepatic steatosis are numerous, and range from progression to chronic liver disease, with its associated morbidity and mortality, to worsening insulin resistance and Type 2 diabetes, as well as being an independent contributor to cardiovascular disease. All such consequences are more likely to occur in patients with Type 2 diabetes who are already at high risk of cardiovascular events. In this article we review the evidence behind the available therapeutic options for hepatic steatosis, and identify challenges and unmet needs in the field.
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PMID:Hepatic steatosis and Type 2 diabetes: current and future treatment considerations. 2143 11

Obesity has reached epidemic proportions and complications related to obesity contribute substantially to both healthcare costs and mortality. Obesity, particularly when accompanied by an excess of visceral/ectopic fat, is a major risk factor for diseases ranging from insulin resistance, type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. The epidemic proportions reached by obesity has made these conditions a global problem in human health. Accordingly, preventive and/or therapeutic interventions should be considered in obese patients. Regular physical activity/exercise has numerous beneficial effects on the cardiometabolic risk profile and on the cardiovascular system. However, our current clinical environment is not designed to provide the regular support needed by patients to help them maintain over the long term their improved physical activity/nutritional habits. Because hypertension, dyslipidemia, hyperinsulinemia, and excess visceral adipose tissue are linked by complex reciprocal molecular interactions, it is logical to expect that targeting an interconnected pathway may provide multiple benefits. At this stage, combined therapy of statins or PPAR agonists and renin-angiotensin-aldosterone system blockers to target multiple therapeutic pathways may optimally improve the cardiometabolic risk profile through both distinct and interrelated mechanisms. In the present article, we will discuss updated novel approaches, including potential multi-targeted intervention strategies, based on underlying pathophysiological processes.
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PMID:Prevention of atherosclerosis in overweight/obese patients. - In need of novel multi-targeted approaches-. 2144 97

Chronic overnutrition and consequential visceral obesity is associated with a cluster of risk factors for cardiovascular disease and type 2 diabetes mellitus. Moreover, individuals who have a triad of hypertension, dysglycemia, and elevated triglycerides along with reduced high-density lipoprotein cholesterol have a greater residual cardiovascular risk even after factoring for the traditional risk factors such as age, smoking, diabetes, and elevated low-density lipoprotein cholesterol. In our previous study we demonstrated that TRC150094, when administered to rats receiving a high-fat diet, stimulated mitochondrial fatty acid oxidation (FAO) and reduced visceral adiposity, opening an interesting perspective for a possible clinical application. In the present study, oral administration of TRC150094 to obese Zucker spontaneously hypertensive fatty rats (obese ZSF1) improved glucose tolerance and glycemic profile as well as attenuated a rise in blood pressure. Obese ZSF1 rats treated with TRC150094 also showed reduced hepatic steatosis, reduced progression of nephropathy, and improved skeletal muscle function. At the cellular level, TRC150094 induced a significant increase in mitochondrial respiration as well as an increased FAO in liver and skeletal muscle, ultimately resulting in reduced hepatic as well as total body fat accumulation, as evaluated by magnetic resonance spectroscopy and magnetic resonance imaging, respectively. If reproduced in humans, these results could confirm that TRC150094 may represent an attractive therapeutic agent to counteract multiple residual cardiovascular risk components.
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PMID:TRC150094 attenuates progression of nontraditional cardiovascular risk factors associated with obesity and type 2 diabetes in obese ZSF1 rats. 2144 17

The metabolic syndrome (MetS) represents a cluster of cardiometabolic risk factors, including central obesity, insulin resistance, glucose intolerance, dyslipidemia, hypertension, hyperinsulinemia and microalbuminuria, and more recently, nonalcoholic fatty liver disease (NAFLD), polycystic ovarian syndrome (PCOS) and atherosclerosis. Although the concept of the MetS is subject to debate due to lack of a unifying underlying mechanism, the prevalence of a metabolic syndrome phenotype is rapidly increasing worldwide. Moreover, it is increasingly prevalent in children and adolescents of obese mothers. Evidence from both epidemiological and experimental animal studies now demonstrates that MetS onset is increasingly likely following exposure to suboptimal nutrition during critical periods of development, as observed in maternal obesity. Thus, the developmental priming of the MetS provides a common origin for this multifactorial disorder. Consequently, the mechanisms leading to this developmental priming have recently been the subject of intensive investigation. This review discusses recent data regarding the epigenetic modifications resulting from nutrition during early development that mediate persistent changes in the expression of key metabolic genes and contribute toward an adult metabolic syndrome phenotype. In addition, this review considers the role of the endogenous molecular circadian clock system, which has the potential to act at the interface between nutrient sensing and epigenetic processing. A continued and greater understanding of these mechanisms will eventually aid in the identification of individuals at high risk of cardiovascular disease (CVD) and type 2 diabetes, and help develop therapeutic interventions, in accordance with current global government strategy.
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PMID:Epigenetic priming of the metabolic syndrome. 2149 73

Viscous soluble fibers have been shown to reduce risk factors associated with type 2 diabetes and cardiovascular disease. The novel functional fiber, PolyGlycopleX (PGX) (InovoBiologic Inc, Calgary, Alberta, Canada) displays greater viscosity than other currently identified soluble fibers. The objective of this study was to determine if PGX lowers serum and hepatic triglycerides (TGs) in a high-sucrose-fed rat model. In this rodent model, feeding a high-sucrose diet consistently increases serum TGs. We hypothesized that consumption of PGX would attenuate hypertriglyceridemia and reduce hepatic steatosis compared with cellulose in rats fed a high-sucrose background diet. Male Sprague-Dawley rats were fed diets containing 65% sucrose and supplemented with either 5% cellulose (control) or 5% PGX (wt/wt) for 43 weeks. At study termination, serum insulin and TGs, hepatic steatosis, and hepatocellular injury were assessed. Body weight increased over time in both groups, but weight gain was attenuated in rats fed PGX vs cellulose in weeks 2 through 22 (P < .05). Serum TGs did not differ from baseline for the first half of the study but consistently increased in the cellulose group thereafter. PolyGlycopleX significantly reduced serum TG to near-baseline levels. At study termination, rats fed PGX had significantly lower hepatic steatosis scores (measured by Sudan black staining) compared with rats fed cellulose. Hepatocellular injury scores did not differ between the groups. In conclusion, PGX reduced serum TG and lipid accumulation in the liver of sucrose-fed rats. Further examination of its potential as a fiber supplement aimed at lessening the burden of hepatic steatosis is warranted.
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PMID:The soluble fiber complex PolyGlycopleX lowers serum triglycerides and reduces hepatic steatosis in high-sucrose-fed rats. 2153 Aug 3

It has been previously observed that low-density lipoprotein receptor knockout (LDLR--/--) mice fed a Western-type diet without cholate and given the liver X receptor agonist T1317 develop a persistent and enhanced hypertriglyceridemia. In contrast, LDLR--/-- mice fed a Paigen diet with cholate exhibit only a transient increase in plasma triglycerides when given T1317. Cholate as an activator of farnesoid X receptor may attenuate T1317-induced triglyceridemia. To determine if cholate was responsible for this transient nature of the hypertriglyceridemia, we orally administered T1317 to LDLR--/-- mice fed a modified Paigen diet without cholate. T1317 transiently elevated plasma triglycerides by increasing plasma very-low-density lipoprotein. Cholesterol and triglyceride levels in plasma very-low-density lipoprotein in T1317-treated mice decreased from peak levels to levels found in vehicle-treated mice after 8 weeks of treatment. A gradual decline of hepatic cholesterol and a transient increase in hepatic triglycerides were also observed in T1317-treated mice. T1317 only transiently activated the expression of genes related to liver de novo lipogenesis, whereas genes related to lipid metabolism were induced in T1317-treated mice, including a gradual increase in plasma lipoprotein lipase activity. Atheroprotective effects of T1317 were observed in the innominate artery and aortic arch but not in the aortic sinus. This work indicates that some component(s) in the Paigen diet other than cholate affect the T1317-induced gene expression profile and ameliorate its effects on lipid synthesis, which lead to hypertriglyceridemia and fatty liver. These findings are important for liver X receptor-related pharmaceutical development for the treatment of cardiovascular disease.
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PMID:The effect of diet on the response of low-density lipoprotein receptor knockout mice to the liver X receptor agonist T1317. 2155 81

The pathogenesis of atherosclerosis has been studied for over a hundred years, but so far no consensus on this issue doesn't exist. During this time, experts have gone from ideas of atherogenesis as a consequence of excess cholesterol in the diet to complex theories of the pathogenesis of atherosclerosis. Today generally accepted that one of the major risk factor for cardiovascular disease and atherosclerosis is dyslipidemia. When atherogenic dyslipidemia occur expressed disbiotic changes intestine and lead to endotoxemia, bacterial translocation and impaired liver function. The undoubted fact is that the liver plays an important role in the development of atherogenic dyslipidemia, and also is the target organ, which leads to the development of nonalcoholic fatty liver disease (NAFLD). Currently, NAFLD is a major risk factor for cardiovascular disease, it limits the possibility of adequate lipid-lowering therapy, increasing cardiovascular risk. Therefore, in the treatment of atherogenic dyslipidemia with statins and fibrates useful purpose hepatoprotectors. Choosing hepatoprotectors depends on the stage NAFLD.
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PMID:[Gastroenterological aspects of atherosclerosis]. 2156 Jun 40


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