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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Detailed studies of hepatic metabolism of lipemic BHE and nonlipemic Wistar rats were conducted. Hepatic lipogenic capacity was varied through the use of starvation or meal feeding. Livers were clamped in precooled copper plates and used for the assay of glycolytic, gluconeogenic, and lipogenic metabolites. Redox and phosphorylation states were calculated. Mitochondrial metabolism was evaluated through studies of the oxygen consumption of isolated mitochondria and through the study of the activities of the alpha-glycerophosphate and malate aspartate shuttles and ATPase. BHE rats have higher phosphorylation states, higher redox ratios, and lower shuttle activities and oxygen consumption by isolated mitochondria than their Wistar cohorts. The differences in oxidative phosphorylation, redox and phosphorylation states, and in the various shuttle activities suggest that BHE liver cells are geared towards lipogenesis at the expense of oxidative phosphorylation. It appears that the activity of the shuttles is controlled in part by phosphorylation state which in turn appears to affect respiration. We theorize from these data that genetically determined differences in the structure and function of the mitochondrial membrane (and perhaps the cell membrane as well) may affect the communication (via metabolites and adenine nucleotides) between the cytosol and mitochondria. Subtle differences in the exchange of metabolites and/or adenine nucleotides across the mitochondrial membrane could thus explain the lipogenic tendency of the liver of the BHE rat and the subsequent development of maturity onset hyperlipemia and hyperglycemia in this strain of rat.
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PMID:Studies on the control of lipogenesis: strain differences in hepatic metabolism. 43 Feb 26

Obesity is known to be associated with diabetes, hypertension and hyperlipidemia in the majority of the patients. There could be inaccuracy in measuring the blood pressure in obesity, therefore a cuff of sufficient size is important in blood pressure measurement. All parameters of obesity have been found to have a correlation with hypertension and it has been suggested that change in weight would cause a change in blood pressure. A weight reduction of 12 kg results in a blood pressure fall of 21/13 mm Hg. Such changes in blood pressures have been noted in untreated hypertensives. A few studies have negated the role of change in weight to have any influence on hypertension. Obesity causes a higher cardiac output and higher blood volume leading to hypertension. There may be increased intracellular sodium and reduced sodium-potassium-ATPase activity in obesity which causes increased sodium loading in hypertension. Abnormalities related to the insulin-carbohydrate metabolism and the renin-angiotensin aldosteron system have also been demonstrated in obese patients. Weight reduction also causes reduced dietary salt intake and diminished sympathetic activity. The benefits of weight reduction appear to be directly related to the amount of weight lost.
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PMID:Effect of obesity and weight reduction in hypertension. 218 Feb 41

The pathogenesis of acute pancreatitis is poorly understood, despite well-recognised precipitating factors. Current evidence suggests that the earliest abnormalities of acute pancreatitis arise within acinar cells, but the key intracellular trigger has yet to be identified. Within the pancreas, physiological concentrations of secretagogues bind to G-protein-linked cell-surface receptors on acinar cells, evoking short, oscillatory spikes of acinar cytosolic-free ionised calcium ([Ca2+]i), an ubiquitous intracellular messenger. Specific effects within acinar cells include initiation of enzyme release through the phosphorylation cascades of stimulus-secretion coupling. Low resting levels of [Ca2+]i are restored by Ca(2+)-ATPase, which pumps calcium into the endoplasmic reticulum and out of the cell. If high concentrations of [Ca2+]i persist, toxicity results, intracellular signalling is disrupted, and cell damage occurs. Sustained elevations in acinar [Ca2+]i result from exposure to high concentrations of secretagogues, high doses of which also induce acute pancreatitis. Similarly, sustained elevations of [Ca2+]i may result from ductal hypertension, alcohol, hypoxia, hypercalcaemia, hyperlipidaemia, viral infection, and various drugs--all factors known to precipitate acute pancreatitis. We suggest that these factors precipitate acute pancreatitis by causing either excessive release of acinar [Ca2+]i, or damage to the integrity of mechanisms that restore low resting levels of [Ca2+]i, and that the consequent calcium toxicity is the key trigger in the pathogenesis of acute pancreatitis.
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PMID:Is an elevated concentration of acinar cytosolic free ionised calcium the trigger for acute pancreatitis? 747 53

Intracellular free calcium activity is in part determined by a calmodulin-regulated plasma membrane Ca(2+)-pump. Since changes in Ca2+ permeability have been implicated in atherosclerotic plaque formation, we initiated a lipid hyperalimentation protocol during which we measured various erythrocyte calcium flux parameters and early atheroma development. Adolescent New Zealand White rabbits were fed a diet with 0.5% cholesterol and 2.5% lard over a 3-month period. Plasma cholesterol and triacylglycerols increased on average 18.7- and 13.9-fold respectively, while erythrocyte membrane cholesterol content decreased 18% and total phospholipids by 54%. After 3 months of lipid hyperalimentation, 22% of the aortic arch was covered with large, early-stage, raised atheroma. Basal and calmodulin-activated (Ca2+ + Mg2+)-ATPase activities in erythrocyte membranes increased by 31% and 123%, respectively at 2 months, with a concomitant increase in calmodulin affinity (Km) from 15.6 to 4.2 nM. These differences were transient on account of changes in the control animals which exhibited a slowly developing sensitivity to calmodulin during maturation. Basal Ca2+ transport and passive Ca2+ permeability increased about 7-fold during the hyperlipidemic phase. This suggests that overt hyperlipidemia, leading to atherosclerotic plaque development, alters plasma membrane Ca2+ regulatory mechanisms including passive Ca2+ permeability. The changes in enzymatic function, membrane composition, and Ca2+ permeability seen in this red cell model system may be a reflection of early changes in cells that are directly involved in the development of atherosclerotic plaques.
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PMID:Regulation of rabbit erythrocyte Ca(2+)-pump sensitivity to calmodulin in experimental hyperlipidemia. 763 51

A nuclear pore complex-associated nucleoside triphosphatase (NTPase) activity is believed to provide energy for nuclear export of poly(A)+ mRNA. This study was initiated to determine if nuclear membrane lipid composition is altered during chronic hyperlipidemia, and what effect this has on NTPase activity. The JCR:LA-cp corpulent rat model is characterized by severe hypertriglyceridemia and moderate hypercholesterolemia, and thus represents an ideal animal model in which to study nuclear cholesterol and NTPase activity. NTPase activity was markedly increased in purified hepatic nuclei from corpulent female JCR:LA-cp rats in comparison to lean control rats as a function of assay time, [GTP], [ATP], and [Mg2+]. Nuclear membrane cholesterol and phospholipid content were significantly elevated in the corpulent animals. Nuclei of corpulent animals were less resistant to salt-induced lysis than nuclei of lean animals, suggesting a change in relative membrane integrity. Together, these results indicate that altered lipid metabolism in a genetic corpulent animal model can lead to changes in nuclear membrane lipid composition, which in turn may alter nuclear membrane NTPase activity and integrity.
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PMID:Nuclear cholesterol content and nucleoside triphosphatase activity are altered in the JCR:LA-cp corpulent rat. 891 86

Several rat models of polycystic kidney disease (PKD) have been published. The only rat model of autosomal dominant polycystic kidney disease currently used is the so-called Hannover rat (Han:SPRD cy/+). This model is characterized by a slow progression of uraemia, proteinuria and hyperlipidaemia. Histological changes clearly resemble those seen is human PKD. The localization of Na+/K(+)-ATPase correlating with the phenotype of the cysts--basal in moderately expanded and apical in highly expanded cysts--suggests that the mislocation of the Na+/K(+)-ATPase is involved in the mechanism of cyst expansion rather than formation, and a consequence of cell dedifferentiation rather than an initial event. Of note is a considerable gender difference in disease severity. Disease anticipation or genetic imprinting does not occur. In addition to gender, a number of interventions influence the progression rate: acceleration is noted after unilateral nephrectomy, the induction of acidosis, chloride feeding or an increased protein intake; slowing down of the course occurs after the induction of alkalosis and castration, and after treatment with lovastatin and methylprednisolone. Thus the Han:SPRD cy/+ rat represents the only well-documented rat model of autosomal dominant PKD resembling a number of features of the human disease.
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PMID:Rat models of autosomal dominant polycystic kidney disease. 904 28

The frequency of cardiovascular diseases in patients with end-stage renal disease (ESRD) is high, since hypotension, hyperlipidemia, advanced age, diabetes and other systemic diseases that may affect the heart are common in such patients. In addition to the pre-existing factors for cardiovascular disease, there are also predisposing factors that relate specifically to life on hemodialysis (HD). These include myocardial stress related to recurrent volume expansion and contraction, anemia, secondary hyperparathyroidism, excess or deficit of certain trace metals that may act as enzyme cofactors, and factors that inhibit myocardial ATPase. The prevalence, pathogenesis, and significance of these factors in ESRD patients are examined, and the potential roles of management are reviewed.
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PMID:Cardiovascular complications in end-stage renal disease and hemodialysis patients. 904 18

To elucidate molecular mechanisms of high fructose-induced metabolic derangements and the influence of peroxisome proliferator-activated receptor-alpha (PPARalpha) activation on them, we examined the expression of sterol regulatory element binding protein-1 (SREBP-1) and PPARalpha as well as its nuclear activation and target gene expressions in the liver of high fructose-fed rats with or without treatment of fenofibrate. After 8-wk feeding of a diet high in fructose, the mRNA contents of PPARalpha protein and its activity and gene expressions of fatty acid oxidation enzymes were reduced. In contrast, the gene expressions of SREBP-1 and lipogenic enzymes in the liver were increased by high fructose feeding. Similar high fructose effects were also found in isolated hepatocytes exposed to 20 mM fructose in the media. The treatment of fenofibrate (30 mg.kg(-1).day(-1)) significantly improved high fructose-induced metabolic derangements such as insulin resistance, hypertension, hyperlipidemia, and fat accumulation in the liver. Consistently, the decreased PPARalpha protein content, its activity, and its target gene expressions found in high fructose-fed rats were all improved by fenofibrate treatment. Furthermore, we also found that the copy number of mitochondrial DNA, the expressions of mitochondrial transcription factor A, ATPase-6 subunit, and uncoupling protein-3 were increased by fenofibrate treatment. These findings suggest that the metabolic syndrome in high fructose-fed rats is reversed by fenofibrate treatment, which is associated with the induction of enzyme expression related to beta-oxidation and the enhancement of mitochondrial gene expression.
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PMID:Amelioration of high fructose-induced metabolic derangements by activation of PPARalpha. 1193 85

Several studies have reported that diabetes may cause limited joint motion and often combines with hyperlipidemia (HL). This study clarifies that joint contracture can be produced by diabetes, HL, or both. The experimental animal model, a rat with diabetes and HL, was developed by streptozosin injection and addition of 1% cholesterol to the food. One hindlimb each from the diabetes group, the HL group, the combined diabetes/HL group, and the control group was immobilized for 2, 3, or 4 weeks in the Phase I study. Diabetes/HL rats were used 4 weeks after immobilization in a Phase II study. Joint motion, elasticity of the knee joint capsule, and contractile function of the gastrocnemius muscle were measured. Gastrocnemius muscle was observed histologically by H&E and ATPase staining. Limited joint mobility was observed 4 weeks after immobilization only in the diabetes/HL group. The intraarticular pressure from the saline injection was lower, and the contractile function of the gastrocnemius muscle decreased in this group. Atrophy of type II fiber was observed in the gastrocnemius muscle. This restriction of joint mobility may depend on skeletal muscle degeneration around the joint rather than on an intraarticular lesion.
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PMID:Diabetes with hyperlipidemia: a risk factor for developing joint contractures secondary to immobility in rat knee joints? 1581 72

Diabetes-induced hyperlipidemia, oxidative stress and protein glycation impair cellular calcium and sodium homeostasis associated with abnormal membrane-bound enzyme activities resulting in cardiac dysfunction in diabetes. To explore the cardioprotective mechanism of green tea in diabetes, we measured the changes in the levels of calcium, sodium, potassium and the activities of Na+/K+ -ATPase and Ca2+ -ATPase in green tea treated diabetic rat hearts. The effect of green tea on triglycerides, lipid peroxidation and protein glycation in diabetic heart were also measured to elucidate the underlying mechanisms. Diabetes was induced by streptozotocin (STZ, 60 mg/kg i.p.). Six weeks after the induction of diabetes, some of the diabetic rats were treated orally with green tea extract (GTE) (300 mg/kg/day) for 4 weeks. GTE produced reduction in blood glucose and lowered the levels of lipid peroxides, triglycerides and extent of protein glycation in the heart of diabetic rats. GTE blunted the rise in cardiac [Ca2+] and [Na+] whereas increased the activities of Ca2+ -ATPase and Na+/K+ -ATPase in diabetic rats. In conclusion, the data provide support to the therapeutic effect of GTE and suggest that a possible mechanism of action may be associated with the attenuation of the rise in [Ca2+] and [Na+] by ameliorating Ca2+ -ATPase and Na+/K+ -ATPase activities.
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PMID:Green tea impedes dyslipidemia, lipid peroxidation, protein glycation and ameliorates Ca2+ -ATPase and Na+/K+ -ATPase activity in the heart of streptozotocin-diabetic rats. 1684 94


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