Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. Obesity is increasingly common among liver transplantation (LT) recipients and donors. Outcomes following LT for selected patients with class I-III obesity are similar to those for nonobese recipients. In patients who are otherwise satisfactory candidates for LT, a high body mass index, as long as it does not present a technical barrier, should not be considered to be an absolute contraindication to LT. 2. The most common causes of death beyond the first year of LT are, in descending order of frequency, graft failure (especially secondary to hepatitis C virus recurrence), malignancy, cardiovascular disease, infections, and renal failure. Metabolic syndrome is an important risk factor for each of these etiologies of posttransplant death. Posttransplant diabetes, posttransplant hypertension, and an original diagnosis of cryptogenic cirrhosis, which is commonly associated with metabolic syndrome, are all associated with an increased risk of post-LT mortality. Features of metabolic syndrome should be screened for and treated in LT recipients. 3. Because of the physiological mechanism of post-LT hypertension, which includes renal arteriolar constriction secondary to calcineurin inhibition, calcium channel blocking agents are a good pharmacological treatment modality and have been shown to be effective in renal protection in randomized controlled trials of posttransplant hypertension. 4. It is rare for dietary changes and weight reduction to result in normalization of the lipid profile. Statins should thus be initiated early in the course of management of post-LT dyslipidemia. Forty milligrams of simvastatin per day, 40 mg of atorvastatin per day, and 20 mg of pravastatin per day are reasonable starting doses for post-LT hypercholesterolemia. It is important to remember that the effects of statin therapy are additive to those of a controlled diet (eg, a Mediterranean diet rich in omega-3 fatty acids, fruits, vegetables, and dietary fiber). 5. Nonalcoholic steatohepatitis, an increasingly common etiology of cirrhosis and liver failure, recurs commonly after LT and may also arise de novo. Treatment should be directed at managing obesity and complications of metabolic syndrome. Optimal immunosuppression in patients with nonalcoholic steatohepatitis is still evolving but should include steroid minimization.
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PMID:Obesity, hyperlipidemia, and metabolic syndrome. 1987 24

Recurrence of the original disease following liver transplantation is not uncommon and can lead to graft failure. There are limited data on recurrent fatty liver disease following liver transplantation. The aim of this study was to determine the incidence of recurrent fatty liver disease in patients with biopsy-proven nonalcoholic steatohepatitis, its effect on survival, and whether there are any predictive factors for recurrence. We analyzed patients undergoing liver transplantation for nonalcoholic steatohepatitis cirrhosis from 1997 to 2008 at a single center. Patients undergoing transplantation for cholestatic disease, alcohol, hepatitis C, or cryptogenic cirrhosis were controls. Ninety-eight patients underwent transplantation for nonalcoholic steatohepatitis cirrhosis. Recurrent fatty liver disease was seen in 70%, 25% had recurrent nonalcoholic steatohepatitis, and 18% had stage II/IV or greater fibrosis at a mean of 18 months. No patients with recurrent nonalcoholic steatohepatitis developed graft failure or required retransplantation at a follow-up of 3 years. No recipient or donor factors were associated with disease recurrence, although patients with recurrent nonalcoholic steatohepatitis had a higher incidence of diabetes, weight gain, and dyslipidemia at the time of diagnosis of recurrence. One-third of patients with recurrent nonalcoholic steatohepatitis had normal liver enzymes at the time of diagnosis post-transplantation. In conclusion, recurrent fatty liver disease is common following liver transplantation for nonalcoholic steatohepatitis cirrhosis but does not lead to early allograft failure. Recurrent nonalcoholic steatohepatitis can occur despite normal liver enzymes, and features of metabolic syndrome are associated with disease recurrence.
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PMID:Recurrent disease following liver transplantation for nonalcoholic steatohepatitis cirrhosis. 1993 17

With increasing survival after orthotopic liver transplantation (OLT), metabolic syndrome and its individual components, including diabetes mellitus, hypertension, dyslipidemia, and obesity, are increasingly being identified and contributing to cardiovascular complications and late morbidity and mortality. The prevalence of posttransplant metabolic syndrome (PTMS) and its individual components has been found to be higher post-OLT versus a comparable population without OLT. The development of nonalcoholic fatty liver disease (NAFLD) after liver transplantation for non-NAFLD cirrhosis is also being increasingly recognized. A number of predictors have been identified as potential risk factors related to these complications. The pretransplant risk factors include immunosuppression, a higher age at transplant, male gender, a history of smoking, the pretransplant body mass index, pre-OLT diabetes, the etiology of the underlying liver disease that resulted in OLT (hepatitis C, cryptogenic cirrhosis, or alcohol), an increased donor body mass index, and marital status. Although there is an increased risk of cardiovascular events, rejection, and infection among patients with PTMS, the overall impact on long-term survival and mortality remains inconclusive. Strategies to reduce the development of metabolic syndrome after transplantation should include lifestyle modifications involving alterations in diet and increased physical activity. Additional measures that may be potentially beneficial include the use of lipid-lowering agents, the optimal control of blood glucose, and the use of tacrolimus instead of cyclosporine.
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PMID:Posttransplant metabolic syndrome: an epidemic waiting to happen. 1993 36

Insulin resistance is the main clinical and pathogenetic feature of the metabolic syndrome, one of the major health problems worldwide. Chronic liver diseases may induce insulin resistance. The hepatic manifestation of the metabolic syndrome is nonalcoholic fatty liver disease. Insulin promotes the storage of energy in the fed state by stimulation of glycogen synthesis, lipogenesis, suppression of gluconeogenesis and VLDL formation. Epidemiological studies have shown that chronic hepatitis C induces insulin resistance. Insulin resistance in chronic hepatitis C is associated with progression of liver fibrosis, resistance to antiviral therapy and development of hepatocellular carcinoma. Here we review the major findings from epidemiological studies from 1994 to the present which have resulted in our current knowledge of insulin resistance in chronic hepatitis C. We further summarise the preliminary pathogenetic models that explain the development of hepatitis C virus-induced insulin resistance. Finally, we draw conclusions for the clinical management of these patients.
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PMID:Insulin resistance in chronic hepatitis C: mechanisms and clinical relevance. 2004 29

Metabolic syndrome comprises a cluster of risk factors that predispose to mainly cardiovascular disease and its complications. It is also closely associated with liver steatosis and fibrosis. Metabolic syndrome and its hepatic manifestation, non-alcoholic fatty liver disease, are very prevalent both in general population and also pre- and post-transplantation setting. Important life-style changes and immunosuppressive treatment after liver transplantation seem to have significant effects for the development of the Metabolic syndrome: increased risks for liver transplant recipients and challenges for successful treatment outcomes. Its association with major vascular events and negative effects on progression of fibrosis in recurrent hepatitis C after transplantation have been major concerns for transplant patients in recent years. There is no standard therapeutic approach to these patients, and well-designed prospective studies are certainly needed to define management strategy. Until such specific data become available, early aggressive risk factor modification should be aimed and each component of the syndrome should be cared separately.
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PMID:Metabolic syndrome and liver transplantation. 2019 31

The incidence of hepatocellular carcinoma is rising due to alcohol drinking, hepatitis C viral infection and metabolic syndrome. Differential expression of CYP2E1 may play a pleiotropic role in the multistep process of liver carcinogenesis. Considerable attention has focused on the antitumor effect of trichostatin A (TSA) as well as CYP2E1 expression-induced apoptosis of cancer cells. However, very few studies have examined the mechanisms by which TSA has an antitumor effect and its association to CYP2E1 expression. The current study examined the action of TSA on CYP2E1 expression and the role of CYP2E1 in inducing apoptosis of HepG2 cells. Our data showed that TSA selectively induced CYP2E1 in four studied human hepatocellular carcinoma (HCC) cell lines (Huh7, PLC/PRF/5, Hep3B and HepG2), but not in normal primary human hepatocytes. TSA-mediated up-regulation of CYP2E1 expression was associated with histone H3 acetylation and the recruitment of HNF-1 and HNF-3beta to the CYP2E1 promoter in HepG2 cells. siRNA-mediated knockdown experiments showed that TSA-induced caspase-3 cleavage was decreased due to reduced expression of CYP2E1 in HepG2 cells. Moreover, down-regulation of CYP2E1 was accompanied by decreased production of mitochondrial reactive oxygen species. These results suggest that histone modification is involved in CYP2E1 gene expression and that CYP2E1-dependent mitochondrial oxidative stress plays a role in TSA-induced apoptosis.
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PMID:Histone modification-mediated CYP2E1 gene expression and apoptosis of HepG2 cells. 2040 16

Nonalcoholic fatty liver disease is increasingly regarded as a hepatic manifestation of metabolic syndrome, and the severity of nonalcoholic fatty liver disease seems to increase in parallel with other features of metabolic syndrome. Excess lipid accumulation in the liver cells is not only a mediator of Metabolic Syndrome and indicator of a lipid overload but also accompanied by a range of histological alterations varying from 'simple' steatosis to nonalcoholic steatohepatitis, with time progressing to manifest cirrhosis. Hepatocellular carcinoma may also occur in nonalcoholic steatohepatitis -related cirrhosis with a mortality rate similar to or worse than for cirrhosis associated with hepatitis C. This review summarizes the knowledge about the causal relationship between hepatic fat accumulation, insulin resistance, liver damage and the etiological role of hepatic fat accumulation in pathogenesis of extra- and intra-hepatic manifestations. Special emphasis is given suggestions of new targets treatment and prevention of nonalcoholic fatty liver disease.
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PMID:The role of hepatic fat accumulation in pathogenesis of non-alcoholic fatty liver disease (NAFLD). 2042 2

The tumor suppressor PTEN is a protein/phosphoinositide phosphatase regulating the PI3K/Akt signaling pathway and is mutated or deleted in a variety of human cancers, including hepatocellular carcinoma (HCC). Accumulating evidence indicates that alterations of PTEN expression and activity in hepatocytes are common and recurrent molecular events associated with liver disorders of various etiologies including obesity, the metabolic syndrome, hepatitis B virus/hepatitis C virus infection and abusive alcohol consumption. Genetic and molecular studies, particularly in the context of non-alcoholic fatty liver disease (NAFLD), support a critical role for PTEN in hepatic insulin sensitivity and the development of steatosis, steatohepatitis and fibrosis. PTEN mutations/deletion or low PTEN expression are also associated with diverse liver malignancies, suggesting a critical role for PTEN in hepatic cancers. This review provides an overview of the current knowledge on pathological dysregulations of PTEN expression/activity in the liver with obesity and the metabolic syndrome, and the role of this enzyme in the development of non-alcoholic fatty liver disease and hepatocellular carcinoma.
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PMID:PTEN in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis and cancer. 2046 Sep 18

Hepatic lipid droplets (LDs) are associated with metabolic syndrome, type 2 diabetes, hepatitis C, and both alcoholic and nonalcoholic fatty liver disease. MicroRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the level of translation. Approximately 1000 different miRNA species are encoded within the human genome, and many are differentially expressed by healthy and diseased liver. However, few studies have investigated the role of miRNAs in regulating LD expression. Accordingly, a high-content assay (HCA) was performed in which human hepatocytes (Huh-7 cells) were transiently transfected with 327 unique human miRNAs; the cells were then fixed, labeled for nuclei and lipid droplets, and imaged with an automated digital microscopy workstation. LD expression was analyzed on a cell-by-cell basis, using automated image analysis. Eleven miRNAs were identified that altered LDs. MiR-181d was the most efficacious inhibitor, decreasing LDs by about 60%. miRNA-181d was also confirmed to reduce cellular triglycerides and cholesterol ester via biochemical assays. Furthermore, a series of proteins was identified via miRNA target analysis, and siRNAs directed against many of these proteins also modified LDs. Thus, HCA-based screening identified novel miRNA and protein regulators of LDs and cholesterol metabolism that may be relevant to hepatic diseases arising from obesity and alcohol abuse.
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PMID:Identification of MicroRNAs that control lipid droplet formation and growth in hepatocytes via high-content screening. 2063

This review of literature and our data suggests that up-regulated production of interferon-gamma (IFNG) in periphery and brain triggers a merger of tryptophan (TRY)-kynurenine (KYN) and guanine-tetrahydrobiopterin (BH4) metabolic pathways into inflammation cascade involved in aging and aging-associated medical and psychiatric disorders (AAMPD) (metabolic syndrome, depression, vascular cognitive impairment). IFNG-inducible KYN/pteridines inflammation cascade is characterized by up-regulation of nitric oxide synthase (NOS) activity (induced by KYN) and decreased formation of NOS cofactor, BH4, that results in uncoupling of NOS that shifting arginine from NO to superoxide anion production. Superoxide anion and free radicals among KYN derivatives trigger phospholipase A2-arachidonic acid cascade associated with AAMPD. IFNG-induced up-regulation of indoleamine 2,3-dioxygenase (IDO), rate-limiting enzyme of TRY-KYN pathway, decreases TRY conversion into serotonin (substrate of antidepressant effect) and increases production of KYN associated with diabetes [xanthurenic acid (XA)], anxiety (KYN), psychoses and cognitive impairment (kynurenic acid). IFNG-inducible KYN/pteridines inflammation cascade is impacted by IFNG (+874) T/A genotypes, encoding cytokine production. In addition to literature data on KYN/TRY ratio (IDO activity index), we observe neopterin levels (index of activity of rate-limiting enzyme of guanine-BH4 pathway) to be higher in carriers of high (T) than of low (A) producers alleles; and to correlate with AAMPD markers (e.g., insulin resistance, body mass index, mortality risk), and with IFN-alpha-induced depression in hepatitis C patients. IFNG-inducible cascade is influenced by environmental factors (e.g., vitamin B6 deficiency increases XA formation) and by pharmacological agents; and might offer new approaches for anti-aging and anti-AAMPD interventions.
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PMID:Interferon-gamma-inducible kynurenines/pteridines inflammation cascade: implications for aging and aging-associated psychiatric and medical disorders. 2081 99


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