Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nonalcoholic fatty liver disease is now recognized as the most common liver disease in the United States, with a prevalence of approximately 5% in the general population and up to 25% to 75% in patients with obesity and type II diabetes mellitus. Nonalcoholic fatty liver disease is a clinicopathologic syndrome with a wide spectrum of histologic abnormalities and clinical outcomes. Hepatic steatosis has a benign clinical course. In contrast, nonalcoholic steatohepatitis (NASH) may progress to cirrhosis and liver-related death in 25% and 10% of patients, respectively. Cases occur most commonly in obese, middle-aged women with diabetes. However, NASH may also occur in children and normal-weight men with normal glucose and lipid metabolism. The pathophysiology involves two steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Although antioxidant therapy with vitamin E is often used, ursodeoxycholic acid is the only drug that has shown benefit and is the most promising of the drugs currently being investigated. Future therapies will depend on a greater understanding of the pathophysiology and should focus on diminishing fibrosis.
 ...
PMID:Update on nonalcoholic fatty liver disease. 1187 8

Nonalcoholic fatty liver disease (NAFLD) is most often associated with obesity, type II Diabetes mellitus, hyperlipidemia and chronic viral hepatitis C. The spectrum of changes encompasses fatty liver, steatohepatitis, liver fibrosis and cirrhosis. Most patients are asymptomatic. The aminotransferases are only slightly elevated (ALT > AST). Grade of inflammation and stage of fibrosis can be assessed accurately only by histologic examination of liver biopsy. In most cases prognosis is favourable but in a subgroup of patients NAFLD may progress to cirrhosis. Recent data suggest that up to 70% of cryptogenic cirrhoses are accounted for by nonalcoholic steatohepatitis. At the moment therapeutic modalities of proven value are not available.
 ...
PMID:[Nonalcoholic fatty liver]. 1193 60

Nonalcoholic fatty liver disease is emerging as the most common liver disease in North America. The histological spectrum of nonalcoholic fatty liver disease ranges from fatty liver alone to steatohepatitis and to the most serious form--nonalcoholic steatohepatitis (NASH). An increasing body of evidence suggests that NASH is associated with the development of progressive fibrosis and eventually cirrhosis in approximately 20% of cases. These data emphasize the need to develop effective therapy for the treatment of NASH. Cases occur most commonly in obese middle age women with diabetes. However, NASH may also occur in children and normal weight men with normal glucose and lipid metabolism. The pathophysiology involves 2 steps. The first is insulin resistance, which causes steatosis. The second is oxidative stress, which produces lipid peroxidation and activates inflammatory cytokines resulting in NASH. Liver biopsy provides prognostic information and identifies NASH patients who may benefit from therapy. Treatment consists of managing the comorbidities: obesity, diabetes, and hyperlipidemia. Nascent clinical trials suggest that a number of therapies may be beneficial. These include anti-oxidants such as vitamin E and betaine, bile acid therapy with ursodeoxycholic acid, and improved insulin sensitivity with metformin. Another potential therapeutic strategy is the reduction of inflammatory cytokines.
 ...
PMID:Diabetes mellitus, obesity, and hepatic steatosis. 1194 30

Insulin resistance results in accumulation of triglyceride content and reduction of glycogen content in skeletal muscle. However, very few studies have measured lipid content and glycogen content in liver associated with insulin resistance. We studied the relationship between liver lipid content, liver glycogen, and insulin resistance in high-fat-fed rats, which are animal models of insulin resistance. High-fat-fed rats were hyperlipidemic, hyperglycemic, and hyperinsulinemic. Furthermore, the glucose infusion rates (GIR) were lower (normal rats, 10.35 +/- 1.66; high-fat-fed rats, 4.86 +/- 0.93 mg/kg/min; P <.01) and the triglyceride and cholesterol contents in liver were higher in the high-fat-fed rats than in normal rats. On the other hand, the glycogen content in liver was lower than in normal rats. There was an inverse relationship between liver triglyceride content and liver glycogen content. When the lipoprotein lipase (LPL) activator NO-1886 was administered to the high-fat-fed rats at a daily dose of 50 mg/kg body weight for 10 weeks, GIR (9.87 +/- 3.76 mg/kg/min, P <.05 v high-fat-fed control group) improved, causing an improvement of the hyperlipidemia, hyperglycemia, and hyperinsulinemia. Furthermore, NO-1886 decreased triglyceride and cholesterol concentrations and increased glycogen content in liver of the high-fat-fed rats. In this study, we found that insulin resistance caused fatty liver and reduced glycogen content in liver. Administration of the LPL activator NO-1886 improved the insulin resistance, resulting in an improvement in the relationship between triglyceride and glycogen content in liver of high-fat-fed rats.
 ...
PMID:Correlation between lipid and glycogen contents in liver and insulin resistance in high-fat-fed rats treated with the lipoprotein lipase activator NO-1886. 1203 38

Nonalcoholic fatty liver disease (NAFLD) includes a wide spectrum of liver injury ranging from simple steatosis to steatohepatitis, fibrosis, and cirrhosis. Whereas simple steatosis has a benign clinical course, steatohepatitis is a recognized cause of progressive liver fibrosis and can develop into cirrhosis. NAFLD and nonalcoholic steatohepatitis (NASH) are the two most common chronic liver diseases in United States general population with a prevalence of 20% and 3%, respectively. Hepatic steatosis is frequently associated with obesity, type 2 diabetes, and hyperlipidemia with insulin resistance as a key pathogenic factor. A two-hit theory best describes the progression from simple steatosis to NASH, fibrosis, or cirrhosis. These two hits consist of the accumulation of excessive hepatic fat primarily owing to insulin resistance, and oxidative stress owing to reactive oxygen species (ROS). Mitochondria are the major cellular source of ROS in cases of NASH. Currently, treatment is focused on modifying risk factors such as obesity, diabetes mellitus, and hyperlipidemia. Antioxidants such as vitamin E, N-acetylcysteine, betaine, and others may be beneficial in the treatment of NASH.
 ...
PMID:Nonalcoholic fatty liver disease: pathogenesis and the role of antioxidants. 1229 56

Nonalcoholic steatohepatitis (NASH), which is the most severe histological form of nonalcoholic fatty liver disease (NAFLD), is emerging as the most common clinically important form of liver disease in developed countries. Although its prevalence is 3% in the general population, this increases to 20-40% in obese patients. Since NASH is associated with obesity, prevalence has been predicted to increase along with the arsent epidemic of obesity and type II diabetes mellitus. The importance of this observation comes from the fact that NASH is a progressive fibrotic disease, in which cirrhosis and liver-related death occur in 25% and 10% in these patients respectively over a 10-year period. This is of particular concern given the increasing recognition of NASH in children. Treatment consists of treating obesity and its co-morbidities; diabetes and hyperlipidemia. Nascent studies suggest that a number of pharmacological therapies may be effective, but all remain unproven at present. Histological and laboratory improvement occurs with a 10% decrease in body weight. Bariatric surgery is indicated in selected patients.A greater understanding of the pathophysiological progression of NASH in obese patients must be obtained in order to develop more focused and improved therapy.
 ...
PMID:Steatohepatitis in obese individuals. 1240 42

Insulin resistant metabolic syndrome is a major clinical disorder including hyperlipidaemia, hypertension, impaired glucose tolerance and/or type 2 diabetes and central obesity, which are well established cardiovascular risk factors. We report the case of a 61-year-old woman who developed severe hypercholesterolaemia and hypertriglyceridaemia after liver transplantation. In her forties she had hypertension, mixed hyperlipidaemia, mild hyperglycaemia and moderate abdominal obesity, suggesting the presence of the metabolic syndrome. She had liver enzyme elevation and severe steatosis and hepatomegaly at ultrasonography. At age 52, cryptogenic liver cirrhosis was diagnosed and rapidly progressing liver failure developed. In 1992 she underwent liver transplantation. Seven years after transplant the patient had abdominal obesity, high blood pressure, marked hypercholesterolaemia, hypertriglyceridaemia and moderate elevation of alanine aminotransferase. She also had impaired glucose tolerance and markedly increased basal and post-glucose load plasma insulin levels. Steatohepatitis was demonstrated by serial liver biopsies. This is the first case that reports the recurrence of the metabolic syndrome following liver transplantation. We postulate that metabolic syndrome may have promoted fatty liver and subsequent progression to end stage liver disease. We also stress the need for careful management of the metabolic syndrome in order to decrease the long-term risk for cardiovascular disease.
 ...
PMID:Recurrence of insulin resistant metabolic syndrome following liver transplantation. 1254 3

Lipid accumulation - in hepatoytes (both subclinically and in acute fatty liver of pregnancy), in the endothelium of placental vessels ("acute atherosis"), and in the bloodstream - has been well established to be a consequence of preeclampsia. Hyperlipidemia (specifically hypertriglyceridemia) has been demonstrated to be a risk factor for the development of preeclampsia. These lipid-related aspects of preeclampsia may appear unrelated, but all are here demonstrated to provide evidence for a causative role for endothelin in the etiology of preeclampsia. Evidence for the potential of endothelin to cause lipid accumulation in hepatocytes and in endothelial cells, by means of activating G protein cascades in these cells, is presented. The capacity of typical free fatty acid constituents of triglycerides to "drive" interacellular G protein cascade-related events is also discussed - which, in this scheme, offers a plausible explanation for hypertriglyceridemia's role as a risk factor for developing preeclampsia. Additional evidence is provided which substantiates endothelin's capacity to cause most of the observed aberrations known to occur in preeclampsia.
 ...
PMID:Cellular bases for the lipid-related aspects of preeclampsia. 1271 Sep 9

We previously generated a strain of transgenic mice carrying the human renin gene, hRN8-12, in the background of C57BL/6j. In this study, we discovered that hRN8-12 male mice, but not females, developed obesity starting at 15 weeks of age. The body weight of 60-week-old male transgenic mice was 2 times higher than that of age-matched wild-type mice. Interestingly, male mice heterozygous for the human renin gene showed moderate weight gain compared with transgenic and wild-type mice. Obese hRN8-12 mice exhibited hyperglycemia, hyperinsulinemia, hyperleptinemia, and hyperlipidemia, and increase in weight in the adipose tissue, liver, heart, and kidneys. Histological analysis demonstrated that fatty hRN8-12 mice developed hypertrophy of pancreatic islets and fatty liver. These results suggested that hRN8-12 mice are associated with obesity dependent on the transgene dosage and should be a genetic model for late-onset obesity.
 ...
PMID:Late-onset obesity in mice transgenic for the human renin gene. 1273 12

We report a new case of hereditary hepatic glycogen synthase (GS) deficiency (MIM 240600) in a French Canadian girl referred at 7 years of age for a family history of hyperlipidemia. Her initial evaluation incidentally revealed fasting hypoglycemia and ketonuria after a 10-hr fast with normal growth, development, and physical examination. Additional biochemical findings included fasting hypoalaninemia with elevated plasma branched chain amino acids and postprandial hyperlactatemia. Liver glycogen synthase activity was reduced. Unlike most other reported patients, we observed on three different occasions an increase in fasting plasma glucose levels after glucagon administration during episodes of hypoglycemia. At 13 years of age, her growth and intellect are normal; however, she still has hypoglycemia after 18 hr of fasting. From our patient's course and a review of the literature, we conclude: (A) Usual modes of presentation of GS deficiency are non-specific symptoms after overnight fasting (7/17), incidental findings (3/17), or positive family history (7/17); (B) Most patients maintain normal growth (8/11) and intellectual abilities (12/15); (C) Fasting hypoglycemia (17/17) and reduced liver glycogen content (9/9) are constant features; (D) Biochemical findings also include postprandial hyperlactatemia (13/13), fasting hyperketonemia (12/12), and fasting hypoalaninemia (8/9); (E) Glucagon response following fasting hypoglycemia is usually reduced or absent (7/8) but can be repeatedly present (1/8); (F) Liver steatosis is frequent (6/6). Although rare, GS deficiency results in a characteristic biochemical profile that, if recognized, should lead promptly to its diagnosis.
 ...
PMID:Long-term follow-up of a new case of liver glycogen synthase deficiency. 1279 86


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>