Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
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Dietary fish oil rich in (n-3) fatty acids plays an important role in reducing abnormalities associated with the metabolic syndrome and mortality from coronary heart disease. We investigated the effects of dietary fish oil on the metabolic syndrome in a high-sucrose-fed rat model. The model was achieved by the administration of 30% sucrose in drinking water in male Wistar rats during 21 weeks. After the metabolic syndrome rat model was established, fish oil was administered during 6 weeks. The metabolic syndrome rats showed significant increases in body weight, systolic blood pressure, serum insulin, total lipids, triacylglycerols, cholesterol, free fatty acids, LDL, total proteins, albumin, and serum tumor necrosis factor-alpha (TNF-alpha). They also presented abdominal and epididymal fat accumulation and fatty liver. After fish oil diet administration, metabolic syndrome rats had a significant reduction in blood pressure, serum insulin, triacylglycerols, cholesterol, free fatty acids, and total lipids, but no change was observed in TNF-alpha concentration or fat accumulation. In conclusion, fish oil reversed the alterations on metabolic parameters and blood pressure exerted by sucrose administration, although it had no effect on TNF-alpha production and adiposity. This confirms the theory that the molecular etiology of the metabolic syndrome is multifactorial, as is the effect of n-3 polyunsaturated fatty acids (PUFAs) upon it, having complex and multifaceted actions.
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PMID:Effects of fish oil on hypertension, plasma lipids, and tumor necrosis factor-alpha in rats with sucrose-induced metabolic syndrome. 1515 41

The insulin resistance syndrome (syndrome X, metabolic syndrome) has become the major health problem of our times. Associated obesity, dyslipidemia, atherosclerosis, hypertension, and type 2 diabetes conspire to shorten life spans, while hyperandrogenism with polycystic ovarian syndrome affect the quality of life and fertility of increasing numbers of women. Whereas a growing number of single genetic diseases affecting satiety or energy metabolism have been found to produce the clinical phenotype, strong familial occurrences, especially in racially prone groups such as those from the Indian subcontinent, or individuals of African, Hispanic, and American Indian descents, together with emerging genetic findings, are revealing the polygenetic nature of the syndrome. However, the strong lifestyle factors of excessive carbohydrate and fat consumption and lack of exercise are important keys to the phenotypic expression of the syndrome. The natural history includes small for gestational age birth weight, excessive weight gains during childhood, premature pubarche, an allergic diathesis, acanthosis nigricans, striae compounded by gynecomastia, hypertriglyceridemia, hepatic steatosis, premature atherosclerosis, hypertension, polycystic ovarian syndrome, and focal glomerulonephritis appearing increasingly through adolescence into adulthood. Type 2 diabetes, which develops because of an inherent and/or an acquired failure of an insulin compensatory response, is increasingly seen from early puberty onward, as is atheromatous disease leading to coronary heart disease and stroke. A predisposition to certain cancers and Alzheimer's disease is also now recognized. The looming tragedy from growing numbers of individuals affected by obesity/insulin resistance syndrome requires urgent public health approaches directed at their early identification and intervention during childhood. Such measures include educating the public on the topic, limiting the consumption of sucrose-containing drinks and foods with high carbohydrate and fat contents, and promoting exercise programs in our nation's homes and schools.
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PMID:Insulin resistance syndrome in children. 1518 Oct 20

Metabolic syndrome also can be named insulin resistance syndrome. The main clinical manifestations include metabolic disorders of glucose and lipid and some diseases caused by the metabolic disorder, such as impaired glucose tolerance or diabetes, obesity, hyperlipemia, fatty liver, hypertension, coronary heart disease, microalbuminuria, etc. According to the theory of zang-fu organs (viscera) in traditional Chinese medicine, these diseases all result from the deficiency of spleen-qi. They are characterized by deficiency in the Ben (root) and excess in the Biao (branch). The Ben (root) is the failure of the spleen in transportation, and the Biao (branch) is stagnation of qi, blood, phlegm, fire, dampness and food. In the prevention and treatment of metabolic syndrome, it is advocated that the intervention of medicine should be used as early as possible, so as to slow down the occurrence and development of insulin resistance, and that emphasis should be transferred from decreasing blood glucose alone to comprehensive prevention of risk factors, especially to the prevention of cardiovascular events. The effect of traditional Chinese herbs is not as good as the western drugs in decreasing the blood pressure and glucose. However, the traditional Chinese herbs have distinctive superiority in ameliorating the insulin resistance, protecting the injury of vascular endothelial cells, regulating the metabolism of lipid, inhibiting the hypercoagulability, and treating the inflammation. Moreover, they are relatively safe. Therefore, the integration of the traditional Chinese medicine and western medicine is worth further research.
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PMID:[Prevention and treatment of metabolic syndrome with integrated traditional Chinese and western medicine]. 1538 69

Hypercholesterolemia is known to enhance the risk of coronary heart disease and fatty liver. Colestimide is an anion-exchange resin, which is not absorbed in the small intestine, decreases the intestinal reabsorption of bile acids synthesized from cholesterol in the liver and consequently increases bile acid excretion into the feces. Bofu-tsusho-san, a traditional Japanese herbal remedy, contains 18 components and has long been used as an anti-obesity agent. In the present study, we investigated the effects of colestimide and/or Bohu-tsusho-san in young male mice fed a high-fat diet. The high-fat diet supplemented with both colestimide and Bofu-tsusho-san markedly reduced the plasma levels of lipids, the liver weight and number of fatty droplets in the liver cytoplasm, and the body growth, compared with animals fed a high-fat diet alone. Neither medicine affected the blood biochemistry. Thus, the hypocholesterolemic action of colestimide, sometimes bringing light flatulence, which is improved by simultaneous administration of Bofu-tsusho-san, which activates the thermogenesis of brown adipose tissue, is suggested to reduce body mass and liver lipids, lowering the plasma levels of lipids.
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PMID:Effects of colestimide and/or Bofu-tsusho-san on plasma and liver lipids in mice fed a high-fat diet. 1627 17

In the United States, elevated serum alanine aminotransferase (ALT) activity in the absence of viral hepatitis or excessive alcohol consumption is most commonly attributed to nonalcoholic fatty liver disease (NAFLD). NAFLD is related to predictors of coronary heart disease (CHD) such as insulin resistance and central obesity. We examined the association between elevated serum ALT activity and the 10-year risk of CHD as estimated using the Framingham risk score (FRS). We performed a cross-sectional analysis comparing participants in the Third National Health and Nutrition Examination Survey with normal and elevated ALT activity (>43 IU/L), examining the mean levels of FRS. Among participants without viral hepatitis or excessive alcohol consumption, those with elevated ALT activity (n=267) had a higher FRS than those with normal ALT activity (n=7259), both among men (mean difference in FRS 0.25, 95% CI 0.07-0.4; hazard ratio for CHD 1.28, 95% CI 1.07-1.5) and women (mean difference in FRS 0.76, 95% CI 0.4-1.1; hazard ratio for CHD 2.14, 95% CI 1.5-3.0). The ALT threshold for increased risk of CHD was higher in men (>43 IU/L) than in women (>30 IU/L). Elevated ALT activity was not associated with higher FRS among nonobese participants with viral hepatitis or excessive alcohol consumption. In condusion, individuals with elevated serum ALT activity in the absence of viral hepatitis or excessive alcohol consumption, most of whom have NAFLD, have an increased calculated risk of CHD. This association is more prominent in women.
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PMID:Elevated serum alanine aminotransferase activity and calculated risk of coronary heart disease in the United States. 1662 37

The development of cholesterol-lowering drugs, including a statins, bile acid sequestrants and cholesterol absorption inhibitors has expanded the options for cardiovascular prevention. Recent treatment guidelines emphasise that individuals at substantial risk for atherosclerotic coronary heart disease should meet defined lipid targets. Combination therapy with drugs that have different and complementary mechanisms of action is often needed to achieve these goals. Existing approaches to the treatment of hypercholesterolaemia are still ineffective in halting the progression of coronary artery disease in some patients despite combination therapies. Other patients are resistant to, or intolerant of, conventional pharmacotherapy and remain at high-risk of atherosclerotic cardiovascular disease, so that alternative approaches are needed. New agents, including inhibitors of microsomal triglyceride transfer protein (MTP), may play a future role, either alone or in combination, in the treatment of hyperlipidaemias. This review focuses on novel approaches to treat dyslipidaemias via the inhibition of MTP. Patients most suitable for use of MTP inhibitors include those with hepatic hypersecretion of apoB, including the metabolic syndrome, Type 2 diabetes mellitus and familial combined hyperlipidaemia, as well as homozygous and heterozygous familial hypercholesterolaemia. However, certain safety issues with these agents need resolving, particularly fatty liver disease.
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PMID:MTP inhibition as a treatment for dyslipidaemias: time to deliver or empty promises? 1722 33

Nonalcoholic fatty liver disease (NAFLD) is associated with several metabolic disturbances involving inflammation. Ultrasensitive C-reactive protein (uCRP), a marker of coronary heart disease and other chronic diseases, has not been investigated in NAFLD. We tested the relationship between uCRP and NAFLD in middle-aged asymptomatic subjects, independently of other metabolic disturbances associated with metabolic syndrome and cardiovascular risk. We compared 310 subjects with steatosis visible on ultrasound (cases) with 630 and without (controls). Body mass index (BMI), blood pressure and serum levels of uCRP, glucose, lipids, and lipoproteins were measured in all subjects. Differences between groups and the impact of serum uCRP levels were tested by univariate and multivariate logistic regression analysis. Cases were statistically different from controls in the frequency of metabolic syndrome (66.4% vs. 26.7%; P < 0.001). Cases were significantly older (P < 0.001), and had significantly higher values for BMI, glucose, total cholesterol and triglycerides (P < 0.001), and mean uCRP concentrations (4.5 vs. 2.79 mg/L; P < 0.001). By univariate analysis, variables significantly associated with cases were glucose (OR, 4.09; 95% CI, 2.98-5.61), BMI (OR 5.54; 95% CI, 4.09-7.49), and uCRP (OR 7.06; 95% CI, 4.51-11.02). By multivariate analysis, uCRP levels were associated with hepatic steatosis (OR 5.83; 95% CI, 3.07-11.06). Cardiovascular risk was also higher in subjects with NAFLD (4.7 vs. 2.8). Subjects with hepatic steatosis showed an increased concentration of uCRP independently of other metabolic disturbances; this suggests an increased risk of cardiovascular diseases and could be used as a marker of chronic inflammation.
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PMID:Association among C-reactive protein, Fatty liver disease, and cardiovascular risk. 1745 97

Elevations in alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT), markers of liver dysfunction and nonalcoholic fatty liver, are considered as part of the metabolic syndrome and related diseases. However, information is limited regarding the persistence (tracking) in levels of these enzymes over time and their influence on cardiovascular (CV) risk in young adults. The study sample consisted of white and black subjects (N = 489, 40% male, 73% white; baseline age, 18-32 years) followed over a period of 12 years as part of the Bogalusa Heart Study, with repeat measurements of CV risk factor variables and liver enzymes. Both at baseline and follow-up, males vs females had higher ALT (P < .01 to .0001) and GGT (P < .0001); blacks vs whites had higher GGT (P < .0001). With respect to persistence in enzyme levels over time, of those individuals who had ALT and GGT at the top quintile specific for age, race, and sex at baseline, about 50% of them continued to remain so with high values after 12 years. Individuals with levels persistently in the highest quintile vs those in the lowest quintile showed higher (P < .0001) body mass index, waist circumference, triglycerides, low-density lipoprotein cholesterol, glucose, insulin, insulin resistance index, and systolic and diastolic blood pressures; lower (P < .0001) high-density lipoprotein cholesterol; and higher (P < .05 to .001) prevalence of obesity, hypertension, dyslipidemia, metabolic syndrome as defined by the National Cholesterol Education Program Adult Treatment Panel III, positive parental history of type 2 diabetes, and coronary heart disease. In addition, based on a multivariate analysis using 2 separate models for ALT and GGT, baseline levels of both enzymes were independent predictors of follow-up; insulin resistance index and baseline GGT were also predictive of follow-up systolic blood pressure. Elevations in liver enzymes ALT and GGT, within "reference" range, persist over time and relate to clinically relevant adverse CV risk profile in young adults.
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PMID:Persistent elevation of liver function enzymes within the reference range is associated with increased cardiovascular risk in young adults: the Bogalusa Heart Study. 1751 12

An outwardly mummified and inwardly badly decomposed body was found in a garage. At autopsy, no injuries were detected. Apart from coronary heart disease, with an old myocardial scar and a hepatic steatosis, the most striking finding was a large intracranial epidural hemorrhage situated at the left frontal lobe. As a relevant traumatic genesis could be ruled out, we deemed this a nontraumatic epidural hematoma. This finding is extremely rare. Several underlying disorders have been discussed as causes of spontaneous epidural hematomas. In this presented case, the authors discuss possible etiological factors.
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PMID:Nontraumatic intracranial epidural hematoma: a case report. 1772 Nov 72

Relationships between fatty liver and coronary heart disease (CHD) and stroke risk remain ill defined. We investigated whether fatty liver is a predictor of CHD and stroke risk. Until December 2000 we followed 2,024 atomic bomb survivors (775 men: 62.0 +/- 9.9 years old; 1,249 women: 63.2 +/- 8.4 years old) who had basic examinations between November 1990 and October 1992 for clinical and laboratory CHD risk factors and fatty liver and who were initially free of CHD and stroke. Forty-nine cases of CHD and 84 cases of stroke were observed. At the time of the baseline examinations, significant clinical associations were found between fatty liver and obesity (p<0.001), hypertension (p<0.001), dyslipidemia (p<0.001), and glucose intolerance (p<0.001). A slight but nonsignificant association was found between fatty liver and hyperuricemia (p=0.07) as well. By using multiple Cox regression analyses, age (relative risk [RR] 1.05, 95% confidence interval [CI] 1.01-1.08), smoking (RR 2.20, 95% CI 1.02-4.74), hyperuricemia (RR 2.30, 95% CI 1.08-4.89), and fatty liver (RR 2.53, 95% CI 1.06-6.06) were shown to be significant predictors of CHD, whereas age (RR 1.08, 95% CI 1.06-1.10), smoking (RR 2.06, 95% CI 1.14-3.72), and hypertension (RR 2.14, 95% CI 1.38-3.30) predicted stroke risk. Fatty liver, which clusters clinical and laboratory CHD risk factors, is an independent predictor of CHD, but not of stroke. Fatty liver should be followed as a feature of metabolic syndrome, with the aim of preventing CHD.
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PMID:Fatty liver and uric acid levels predict incident coronary heart disease but not stroke among atomic bomb survivors in Nagasaki. 1803 75


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