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)

High fructose consumption is associated with the development of fatty liver and dyslipidemia with poorly understood mechanisms. We used a matrix-assisted laser desorption/ionization-based proteomics approach to define the molecular events that link high fructose consumption to fatty liver in hamsters. Hamsters fed high-fructose diet for 8 weeks, as opposed to regular-chow-fed controls, developed hyperinsulinemia and hyperlipidemia. High-fructose-fed hamsters exhibited fat accumulation in liver. Hamsters were killed, and liver tissues were subjected to matrix-assisted laser desorption/ionization-based proteomics. This approach identified a number of proteins whose expression levels were altered by >2-fold in response to high fructose feeding. These proteins fall into 5 different categories including (1) functions in fatty acid metabolism such as fatty acid binding protein and carbamoyl-phosphate synthase; (2) proteins in cholesterol and triglyceride metabolism such as apolipoprotein A-1 and protein disulfide isomerase; (3) molecular chaperones such as GroEL, peroxiredoxin 2, and heat shock protein 70, whose functions are important for protein folding and antioxidation; (4) enzymes in fructose catabolism such as fructose-1,6-bisphosphatase and glycerol kinase; and (5) proteins with housekeeping functions such as albumin. These data provide insight into the molecular basis linking fructose-induced metabolic shift to the development of metabolic syndrome characterized by hepatic steatosis and dyslipidemia.
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PMID:Proteomic analysis of fructose-induced fatty liver in hamsters. 1864 Mar 90

Hypertriglyceridemia is observed in many metabolic diseases such as the metabolic syndrome, diabetes mellitus, or mixed dyslipidemia frequently leading to premature coronary heart disease (CHD). Additionally, several studies have shown that postprandial hypertriglyceridemia is pronounced in patients with CHD, metabolic syndrome, hypertension, and other pathologic conditions. The triglyceride-rich lipoprotein remnants accumulating in the postprandial state seem to be involved in atherogenesis and in events leading to thrombosis. Since abnormal postprandial lipemia is associated with pathologic conditions, its treatment is of clinical importance.Fibrates are of significant help in managing hypertriglyceridemia. This review summarizes the effect of fibric acid derivatives on postprandial lipemia. Fibrates decrease the production of and enhance the catabolism of triglyceride-rich lipoproteins through the activation of peroxisome proliferator-activated receptor-alpha. Results of clinical studies with fibrates have confirmed their action in decreasing postprandial triglyceride levels by increasing lipoprotein lipase activity, decreasing apolipoprotein CIII production, and by increasing fatty acid oxidation in the liver.It is concluded that fibrates are effective agents in lowering the postprandial increase in remnant lipoprotein particles and retinyl palmitate. Furthermore, fibrates can also affect the postprandial lipid profile by increasing hepatic lipase levels and in some cases, by reducing cholesterol ester transfer protein activity. The main target of fibrate therapy is to improve fasting hypertriglyceridemia, which is an essential component associated with improving postprandial lipemia. Fibrates are well tolerated by patients and adverse effects have been reported rarely after their administration.
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PMID:Therapeutic effects of fibrates in postprandial lipemia. 1869 Jul 58

In an elderly pool of 3288 subjects (65-84 years of age), taking part in the Italian Longitudinal Studies on Aging (ILSA). We evaluated the prevalence of acute myocardial infarction (AMI), the stroke, the non-fatal AMI+stroke cases in relation to the larger or smaller values of the apolipoprotein-B (Apo-B) level considered as cutoff point of normality (150 mg/100 ml). In addition, during the follow-up of 3 years, we observed the prevalence of all these pathologies (AMI, stroke, non-fatal AMI+stroke) in the subjects who had none of these syndromes at the start of the study period. At last, we studied the percentual occurrence of the parameters indicated by the IDF as signs of the metabolic syndrome (MS), and compared them between the subjects displaying higher or lower values of Apo-B of the normal level. Our results revealed that the Apo-B value may be considered as a predictive factor of lipidemic, atherogenic alterations, and it merits in this sense to be included in the diagnostic criteria of MS. However, it cannot be considered as an independent factor of preventive diagnosis of the non-fatal cardio-cerebrovascular complications.
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PMID:The significance of apolipoprotein-B (Apo-B) in the elderly as a predictive factor of cardio-cerebrovascular complications. 1870 Nov 71

The endocannabinoid pathway plays an important role in the regulation of appetite and body weight, hepatic lipid metabolism, and fibrosis. Blockade of the endocannabinoid receptor CB1 with SR141716 promotes weight loss, reduces hepatocyte fatty acid synthesis, and is antifibrotic. D-4F, an apolipoprotein A-1 mimetic with antioxidant properties, is currently in clinical trials for the treatment of atherosclerosis. C57BL/6J mice were fed a high-fat diet for 7 months, followed by a 2.5-month treatment with either SR141716 or D-4F. SR141716 markedly improved body weight, liver weight, serum transaminases, insulin resistance, hyperglycemia, hypercholesterolemia, hyperleptinemia, and oxidative stress, accompanied by the significant prevention of fibrosis progression. D-4F improved hypercholesterolemia and hyperleptinemia without improvement in body weight, steatohepatitis, insulin resistance, or oxidative stress, and yet, there was significant prevention of fibrosis. D-4F prevented culture-induced activation of stellate cells in vitro. In summary, C57BL/6J mice given a high-fat diet developed features of metabolic syndrome with nonalcoholic steatohepatitis and fibrosis. Both SR141716 and D-4F prevented progression of fibrosis after onset of steatohepatitis, ie, a situation comparable to a common clinical scenario, with D-4F seeming to have a more general antifibrotic effect. Either compound therefore has the potential to be of clinical benefit.
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PMID:Prevention of hepatic fibrosis in a murine model of metabolic syndrome with nonalcoholic steatohepatitis. 1877 30

Plasma levels of lipoproteins that contain apolipoprotein (apo) CIII predict coronary heart disease (CHD), and associate with contributors to metabolic syndrome such as type 2 diabetes and hypertriglyceridemia. ApoCIII causes hypertriglyceridemia by inhibiting the catabolism and the clearance of TG-rich lipoproteins (TLRs), and the association of apoCIII with CHD has been commonly attributed to these properties; however, it has been untested whether apoCIII itself or in association with lipoproteins directly affects atherogenic mechanisms in vascular cells. This review describes the proatherogenic effect of apoCIII-containing lipoproteins. In brief, apoCIII-rich VLDL (VLDL CIII+) increased the adhesion of human monocytes to vascular endothelial cells (ECs). ApoCIII alone also increased monocyte adhesion to vascular ECs. Interestingly, apoCIII-rich HDL did not reduce the adhesion of monocytes to vascular ECs, whereas HDL without apoCIII decreased their adhesion, suggesting that apoCIII in HDL counteracts the anti-inflammatory property of HDL. ApoCIII alone as well as VLDL CIII+also activated vascular ECs through the activation of NF-kappaB, and induced the recruitment of monocytes to vascular ECs. Moreover, apoCIII induced insulin resistance in vascular ECs and caused endothelial dysfunction. These findings indicate that apoCIII in TLRs not only modulates their metabolism, but also may directly contribute to the development of atherosclerosis by activating the proinflammatory signal transduction of vascular cells. Here, we propose a novel role for apoCIII that links dyslipidemia with atherosclerosis.
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PMID:Apolipoprotein CIII links dyslipidemia with atherosclerosis. 1926 4

Elevated apolipoprotein (apo) B-100 is a common abnormality in insulin-resistant subjects with obesity and type 2 diabetes mellitus that increases risk of cardiovascular disease. ApoB-100 metabolism is complex. Kinetic studies using stable isotope tracer have provided useful mechanistic insight into its therapeutic regulation. Dysregulation of apoB-100 metabolism is integral to dyslipidaemia in the metabolic syndrome (MetS). This is dynamically related to a combination of overproduction of very-low density lipoprotein apoB-100 and decreased catabolism of apoB-containing particles, with accelerated catabolism of high-density lipoprotein (HDL) particles. These abnormalities may be consequent on a global effect of insulin resistance and accumulation of visceral and liver fat. Several therapeutic interventions, such as weight loss, physical exercise, statins, fibrates, fish oils and cholesteryl ester transfer protein inhibitors can correct apoB-100 metabolism in MetS. This encapsulates several kinetic mechanisms of action, including decreased secretion of apoB-100, increased catabolism of apoB-100 and delayed catabolism of HDL particles. Other agents, including cholesterol absorption inhibitors, niacins, and endocannabinoid-1 receptor blockers, have also been shown to improve plasma lipid and lipoprotein abnormalities in insulin resistance; their mechanisms of action require further investigation in MetS. The complementary mechanisms of action of different therapies support the use of combination regimens to treat dyslipoproteinaemia in MetS, including type 2 diabetes. Tracer methodology is a powerful tool to evaluate established and new lipid-regulating therapies.
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PMID:Therapeutic regulation of apoB100 metabolism in insulin resistance in vivo. 1949 Sep 28

Hyperuricemia is a common finding in hypertensive patients, especially among those who are on diuretic therapy. However, its clinical relevance regarding cardiovascular and chronic kidney disease (CKD) has not clearly been established. The authors assessed whether, in a population of 385 hypertensive women categorized according to diuretic therapy, the stratification in quartiles by uric acid levels would identify a gradient of changes in renal function and in risk factors for cardiovascular disease. The following were evaluated: serum uric acid, glycemia, total and fractional cholesterol, triglycerides, apolipoprotein (Apo) B, Apo A-I, and C-reactive protein. Renal function was assessed by serum creatinine, albuminuria, and estimated glomerular filtration rate (eGFR) by the Modification of Diet in Renal Disease equation, whereas cardiovascular risk was estimated through the Framingham score. A total of 246 women were on diuretic therapy; 139 were taking other antihypertensive medications. There was a reduction in eGFR parallel to the increase in uric acid levels, regardless of diuretic use and without a concomitant increase in albuminuria. In both groups, higher uric acid levels translated into an increase in metabolic syndrome components, in markers of insulin resistance, triglyceride / high-density lipoprotein levels, and Apo B/Apo A-I ratios, as well as in Framingham scores. Hyperuricemia was associated with an increase in inflammatory markers only in patients on diuretic therapy. In a binary logistic regression, hyperuricemia (uric acid >6.0 mg/ dL) was independently associated with CKD (eGFR <60 mL/ min / 1.73 m(2)) (odds ratio, 2.63; 95% confidence interval, 1.61-4.3; P<.001). In hypertensive women, the presence of hyperuricemia indicated a substantial degree of kidney dysfunction as well as a greater cardiovascular risk profile.
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PMID:Uric acid as a marker for renal dysfunction in hypertensive women on diuretic and nondiuretic therapy. 1953 22

Trans-11 vaccenic acid (VA) is the predominant trans isomer in ruminant fat and a major precursor to the endogenous synthesis of cis9,trans11-conjugated linoleic acid in humans and animals. We have previously shown that 3-wk VA supplementation has a triglyceride (TG)-lowering effect in a rat model of dyslipidemia, obesity, and metabolic syndrome (JCR:LA-cp rats). The objective of this study was to assess the chronic effect (16 wk) of VA on lipid homeostasis in both the liver and intestine in obese JCR:LA-cp rats. Plasma TG (P < 0.001), total cholesterol (P < 0.001), LDL cholesterol (P < 0.01), and nonesterified fatty acid concentrations, as well as the serum haptoglobin concentration, were all lower in obese rats fed the VA diet compared with obese controls (P < 0.05). In addition, there was a decrease in the postprandial plasma apolipoprotein (apo)B48 area under the curve (P < 0.05) for VA-treated obese rats compared with obese controls. The hepatic TG concentration and the relative abundance of fatty acid synthase and acetyl-CoA carboxylase proteins were all lower (P < 0.05) in the VA-treated group compared with obese controls. Following acute gastrointestinal infusion of a VA-triolein emulsion in obese rats that had been fed the control diet for 3 wk, the TG concentration was reduced by 40% (P < 0.05) and the number of chylomicron (CM) particles (apoB48) in nascent mesenteric lymph was reduced by 30% (P < 0.01) relative to rats infused with a triolein emulsion alone. In conclusion, chronic VA supplementation significantly improved dyslipidemia in both the food-deprived and postprandial state in JCR:LA-cp rats. The appreciable hypolipidemic benefits of VA may be attributed to a reduction in both intestinal CM and hepatic de novo lipogenesis pathways.
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PMID:Trans-11 vaccenic acid reduces hepatic lipogenesis and chylomicron secretion in JCR:LA-cp rats. 1975 43

Apolipoprotein A5 gene (APOA5) variants are associated with increased plasma triglycerides, a risk factor for the metabolic syndrome (MS), but a correlation with apolipoprotein C3 (APOC3) genotypes is controversial. We investigated the correlation of APOA5 genotypes with plasma apoA5 levels and APOC3 genotypes in MS patients from a Romanian population. APOA5 (-1131T>C, c.56C>G) and APOC3 (-482C>T, -455T>C) genotypes and plasma apoA5 concentration were determined in MS patients and healthy subjects. Results showed higher apoA5 levels in plasma and high density lipoproteins (HDL) from MS patients, carriers of the APOA5 c.56G allele, as compared to MS carriers of APOA5 -1131C allele or the common genotype. ApoA5 levels in plasma and HDL fraction from MS carriers of -1131C and c.56G alleles correlated positively with plasma triglycerides levels and negatively with HDL-cholesterol in MS carriers of c.56G allele. Higher frequencies of APOC3 -482T and -455C alleles were detected in MS patients compared with healthy subjects. We demonstrated the association of APOC3 -482T and -455C with APOA5 -1131C allele, but not with c.56G allele in MS patients. We propose APOA5c.56C>G as a functional polymorphism, whereas APOA5 -1131T>C is not an independent risk factor, being effective only when associated with APOC3 -482T or -455C alleles.
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PMID:Association of APOA5 and APOC3 gene polymorphisms with plasma apolipoprotein A5 level in patients with metabolic syndrome. 1993 84

To compare the molecular composition and functional differences at the lipoprotein level, we analyzed individual lipoprotein fractions from male patients with metabolic syndrome (MetS) (n=10) and gender- and age-matched healthy controls (n=14). The MetS group had significantly higher obesity, blood pressure, serum cholesterol, triglyceride (TG), adiponectin, and uric acid levels than the control group, while the serum blood urea nitrogen and creatinine levels of the MetS group were in the normal range. The MetS group had much weaker serum antioxidant ability and were more susceptible to copper-mediated low-density lipoprotein (LDL)-oxidation. TG and apoC-III co-accumulated with LDL, high density lipoprotein (HDL)2, and HDL3 in the MetS group. The MetS group had serum amyloid A (SAA)-enriched HDL2 and HDL3, although the serum level of SAA was not higher than in controls. The MetS group had significantly deprived paraoxonase (PON) activity in the serum and HDL, while the MetS group had 38% higher serum cholesteryl ester transfer protein (CETP) activity than that of the control group. Many serum parameters, such as TG, apoC-III, and uric acid, were elevated in the MetS group, and most of these measures were enriched in the LDL and HDL fractions rather than the very low density lipoprotein (VLDL) fraction. The lipid and apolipoprotein composition of HDL was severely altered and its beneficial functions were severely diminished. ApoA-I level was more readily detected in lipoprotein-deficient serum of the MetS group, indicating that the apoA-I exists in a lipid-free state. These results suggest that the MetS group had dysfunctional HDL that enriched TG, apoC-III, CETP, and SAA without antioxidant activity.
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PMID:The functional and compositional properties of lipoproteins are altered in patients with metabolic syndrome with increased cholesteryl ester transfer protein activity. 1995 11


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