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Query: UMLS:C0242339 (dyslipidemia)
 13,927 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fructose (FR) feeding in rats provides a model of dietary-induced insulin resistance that has been used to examine interactions among the cluster of metabolic disorders including insulin resistance, hyperinsulinemia, hypertension, and dyslipidemia known as Syndrome X. In animals with reduced beta-cell mass, however, insulin resistance may not have similar associated disorders. Therefore this study examined the consequences of FR feeding in rats with a reduced beta-cell mass. Formerly diabetic islet-transplanted (TX) or shamoperated (SHAM) male Wistar Furth rats were fed a purified control (CNTL) diet or a diet containing either 40 or 70% (wt/wt) FR for 3-5 wk. FR feeding in SHAM animals resulted in elevated triglyceride levels but did not affect fed or fasting glucose and insulin concentrations, blood pressure, glucose tolerance, and the acute insulin response to a glucose bolus compared with CNTL-fed animals. Among TX animals, hypertriglyceridemia and fasting hyperglycemia were observed only in those fed FR. Thus the effects of diet-induced insulin resistance are limited to dyslipidemia, if insulin secretory capacity is adequate, but are detrimental to both glucose and lipid metabolism in combination with a reduced beta-cell mass.
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PMID:Consequences of high dietary fructose in the islet-transplanted rat with suboptimal beta-cell mass. 877 51

Cholesteryl ester transfer protein (CETP) plays a pivotal role in the reverse transport of cholesterol and in the remodeling of circulating lipoproteins. While plasma and adipose tissue levels of CETP are affected by a variety of metabolic conditions, the extent of the effects of dietary factors, other than high cholesterol feeding, are not well understood. To further explore this paradigm, male Golden Syrian hamsters were fed for 4 weeks with a 60%-enriched fructose diet (F) and were compared to a matched group of animals fed with a normal chow diet (N). After feeding for 4 weeks, plasma insulin concentrations were lower in animals fed fructose than in control animals (F: 3.3+/-0.8 vs N: 7.4+/-1.9 ng/mL; p<0.03), but there was no significant difference in plasma glucose concentrations between the two groups (F: 138+/-7 vs N: 148+/-10 mg/dL; p>0.05). Fructose-fed animals showed significant increases in plasma triglyceride (F: 269+/-22 vs N: 165+/-22 mg/dL; p<0.01) and plasma cholesterol (F: 150+/-10 vs N: 113+/-6 mg/dL; p<0.02) concentrations compared with control animals. Total CETP activity and immunoreactive mass were higher in the plasma of fructose-fed animals that in that of controls (F: 1036+/-70 vs N: 826+/-43 pmol/h/mL, p<0.04 and F: 24.5+/-3.1 vs N: 37.5+/-4.3 AU, p<0.02, respectively). Adipose tissue CETP mRNA levels, assessed by the very sensitive ribonuclease protection assay, were 53% higher in fructose-fed animals than in controls (F: 14.1+/-2.0 vs N: 9.2+/-1.0 AU over a rRNA control; p<0.04). Adipose tissue CETP activity and immunoreactive mass also showed a statistically significant increase in the fructose-fed hamsters compared with those fed a normal diet (p<0.04). In conclusion, fructose feeding in Syrian hamsters induces a mixed dyslipidemia. These metabolic changes are accompanied by a significant increase in CETP levels, both in plasma and in adipose tissue. This phenomenon suggests that the increase in the expression of adipose tissue CETP may be caused either by the ambient hypercholesterolemia resulting from fructose feeding or by an attenuation of a possible inhibitory effect of plasma insulin concentrations on the expression of adipose tissue CETP in this feeding paradigm.
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PMID:Induction of cholesteryl ester transfer protein in adipose tissue and plasma of the fructose-fed hamster. 1147 89

Obesity and type 2 diabetes are occurring at epidemic rates in the United States and many parts of the world. The "obesity epidemic" appears to have emerged largely from changes in our diet and reduced physical activity. An important but not well-appreciated dietary change has been the substantial increase in the amount of dietary fructose consumption from high intake of sucrose and high fructose corn syrup, a common sweetener used in the food industry. A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, perturbs glucose metabolism and glucose uptake pathways, and leads to a significantly enhanced rate of de novo lipogenesis and triglyceride (TG) synthesis, driven by the high flux of glycerol and acyl portions of TG molecules from fructose catabolism. These metabolic disturbances appear to underlie the induction of insulin resistance commonly observed with high fructose feeding in both humans and animal models. Fructose-induced insulin resistant states are commonly characterized by a profound metabolic dyslipidemia, which appears to result from hepatic and intestinal overproduction of atherogenic lipoprotein particles. Thus, emerging evidence from recent epidemiological and biochemical studies clearly suggests that the high dietary intake of fructose has rapidly become an important causative factor in the development of the metabolic syndrome. There is an urgent need for increased public awareness of the risks associated with high fructose consumption and greater efforts should be made to curb the supplementation of packaged foods with high fructose additives. The present review will discuss the trends in fructose consumption, the metabolic consequences of increased fructose intake, and the molecular mechanisms leading to fructose-induced lipogenesis, insulin resistance and metabolic dyslipidemia.
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PMID:Fructose, insulin resistance, and metabolic dyslipidemia. 1572 2

High-fructose diet stimulates hepatic de novo lipogenesis (DNL) and causes hypertriglyceridemia and insulin resistance in rodents. Fructose-induced insulin resistance may be secondary to alterations of lipid metabolism. In contrast, fish oil supplementation decreases triglycerides and may improve insulin resistance. Therefore, we studied the effect of high-fructose diet and fish oil on DNL and VLDL triglycerides and their impact on insulin resistance. Seven normal men were studied on four occasions: after fish oil (7.2 g/day) for 28 days; a 6-day high-fructose diet (corresponding to an extra 25% of total calories); fish oil plus high-fructose diet; and control conditions. Following each condition, fasting fractional DNL and endogenous glucose production (EGP) were evaluated using [1-13C]sodium acetate and 6,6-2H2 glucose and a two-step hyperinsulinemic-euglycemic clamp was performed to assess insulin sensitivity. High-fructose diet significantly increased fasting glycemia (7 +/- 2%), triglycerides (79 +/- 22%), fractional DNL (sixfold), and EGP (14 +/- 3%, all P < 0.05). It also impaired insulin-induced suppression of adipose tissue lipolysis and EGP (P < 0.05) but had no effect on whole- body insulin-mediated glucose disposal. Fish oil significantly decreased triglycerides (37%, P < 0.05) after high-fructose diet compared with high-fructose diet without fish oil and tended to reduce DNL but had no other significant effect. In conclusion, high-fructose diet induced dyslipidemia and hepatic and adipose tissue insulin resistance. Fish oil reversed dyslipidemia but not insulin resistance.
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PMID:Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy men. 1598 89

A novel animal model of insulin resistance, the fructose-fed Syrian golden hamster, was employed to investigate the efficacy and mechanisms of action of rosuvastatin, a HMG-CoA reductase inhibitor, in ameliorating metabolic dyslipidemia in insulin-resistant states. Fructose feeding for a 2-week period induced insulin resistance and a significant increase in hepatic secretion of VLDL. This was followed by a fructose-enriched diet with or without 10 mg/kg rosuvastatin for 14 days. Fructose feeding in the first 2 weeks caused a significant increase in plasma total cholesterol and triglyceride in both groups (n=6, p<0.001). However, there was a significant decline (30%, n=8, p<0.05) in plasma triglyceride levels following rosuvastatin feeding (10 mg/kg). A significant decrease (n=6, p<0.05) was also observed in VLDL-apoB production in hepatocytes isolated from drug-treated hamsters, together with an increased apoB degradation (n=6, p<0.05). Similar results were obtained in parallel cell culture experiments in which primary hepatocytes were first isolated from chow-fed hamsters, and then treated in vitro with 15 microM rosuvastatin for 18 h. Rosuvastatin at 5 microM caused a substantial reduction in synthesis of unesterified cholesterol and cholesterol ester (98 and 25%, n=9, p<0.01 or p<0.05) and secretion of newly synthesized unesterified cholesterol, cholesterol ester, and triglyceride (95, 42, and 60% reduction, respectively, n=9, p<0.01 or p<0.05). This concentration of rosuvastatin also caused a significant reduction (75% decrease, n=4, p<0.01) in the extracellular secretion of VLDL-apoB100, accompanied by a significant increase in the intracellular degradation of apoB100. There was a 12% reduction (not significant, p>0.05) in hepatic MTP and no changes in ER-60 (a chaperone involved in apoB degradation) protein levels. Taken together, these data suggest that the assembly and secretion of VLDL particles in hamster hepatocytes can be acutely inhibited by rosuvastatin in a process involving enhanced apoB degradation. This appears to lead to a significant amelioration of hepatic VLDL-apoB overproduction observed in the fructose-fed, insulin-resistant hamster model.
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PMID:Effect of rosuvastatin on hepatic production of apolipoprotein B-containing lipoproteins in an animal model of insulin resistance and metabolic dyslipidemia. 1600 78

Fructose feeding has been shown to induce insulin resistance in rats, associated with hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. We have investigated the effect of administering food seasoning spices mixture (SM) on glucose, insulin, and lipids in circulation and carbohydrate enzymes in the erythrocytes of high fructose-fed rats. Additionally, we also measured the protein glycation status by assaying the levels of glycated hemoglobin, fructosamine, and plasma protein glycation. Male Wistar rats received a daily diet containing either 60% fructose or 60% starch (control). The rats were administered SM at three different doses (10, 30, or 50 mg/day per rat) orally 15 days later. At the end of the 45-day experimental period, fructose-fed rats showed significantly higher levels of plasma glucose and insulin, dyslipidemia, and alterations in enzyme activities. Treatment with SM significantly reduced plasma glucose and insulin levels and brought about a favorable lipid profile. In these rats, the activities of enzymes of glucose metabolism were normal. These effects were observed at all three doses of SM. High homeostasis model assessment (HOMA) values indicated insulin resistance in fructose-fed rats, while the HOMA values in SM-treated fructose-fed rats were comparable to those of control rats. We conclude that administration of SM improves glucose metabolism and plasma lipid profile in fructose-fed rats, possibly through improved insulin-sensitizing actions of the active constituents.
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PMID:Food seasoning spices mixture improves glucose metabolism and lipid profile in fructose-fed hyperinsulinemic rats. 1637 62

Increased dietary fructose in rodents recapitulates many aspects of the Metabolic Syndrome with hypertension, insulin resistance and dyslipidemia. Here we show that fructose increased jejunal NaCl and water absorption which was significantly decreased in mice whose apical chloride/base exchanger Slc26a6 (PAT1, CFEX) was knocked out. Increased dietary fructose intake enhanced expression of this transporter as well as the fructose-absorbing transporter Slc2a5 (Glut5) in the small intestine of wild type mice. Fructose feeding decreased salt excretion by the kidney and resulted in hypertension, a response almost abolished in the knockout mice. In parallel studies, a chloride-free diet blocked fructose-induced hypertension in Sprague Dawley rats. Serum uric acid remained unchanged in animals on increased fructose intake with hypertension. We suggest that fructose-induced hypertension is likely caused by increased salt absorption by the intestine and kidney and the transporters Slc26a6 and Slc2a5 are essential in this process.
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PMID:Fructose-induced hypertension: essential role of chloride and fructose absorbing transporters PAT1 and Glut5. 1867 Apr 4

While virtually absent in our diet a few hundred years ago, fructose has now become a major constituent of our modern diet. Our main sources of fructose are sucrose from beet or cane, high fructose corn syrup, fruits, and honey. Fructose has the same chemical formula as glucose (C(6)H(12)O(6)), but its metabolism differs markedly from that of glucose due to its almost complete hepatic extraction and rapid hepatic conversion into glucose, glycogen, lactate, and fat. Fructose was initially thought to be advisable for patients with diabetes due to its low glycemic index. However, chronically high consumption of fructose in rodents leads to hepatic and extrahepatic insulin resistance, obesity, type 2 diabetes mellitus, and high blood pressure. The evidence is less compelling in humans, but high fructose intake has indeed been shown to cause dyslipidemia and to impair hepatic insulin sensitivity. Hepatic de novo lipogenesis and lipotoxicity, oxidative stress, and hyperuricemia have all been proposed as mechanisms responsible for these adverse metabolic effects of fructose. Although there is compelling evidence that very high fructose intake can have deleterious metabolic effects in humans as in rodents, the role of fructose in the development of the current epidemic of metabolic disorders remains controversial. Epidemiological studies show growing evidence that consumption of sweetened beverages (containing either sucrose or a mixture of glucose and fructose) is associated with a high energy intake, increased body weight, and the occurrence of metabolic and cardiovascular disorders. There is, however, no unequivocal evidence that fructose intake at moderate doses is directly related with adverse metabolic effects. There has also been much concern that consumption of free fructose, as provided in high fructose corn syrup, may cause more adverse effects than consumption of fructose consumed with sucrose. There is, however, no direct evidence for more serious metabolic consequences of high fructose corn syrup versus sucrose consumption.
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PMID:Metabolic effects of fructose and the worldwide increase in obesity. 2008 73

The large daily energy intake common among athletes can be associated with a large daily intake of fructose, a simple sugar that has been linked to metabolic disorders. Fructose commonly is found in foods and beverages as a natural component (e.g., in fruits) or as an added ingredient (as sucrose or high fructose corn syrup [HFCS]). A growing body of research suggests that excessive intake of fructose (e.g., >50 g.d(-1)) may be linked to development of the metabolic syndrome (obesity, dyslipidemia, hypertension, insulin resistance, proinflammatory state, prothrombosis). The rapid metabolism of fructose in the liver and resultant drop in hepatic adenosine triphosphate (ATP) levels have been linked with mitochondrial and endothelial dysfunction, alterations that could predispose to obesity, diabetes, and hypertension. However, for athletes, a positive aspect of fructose metabolism is that, in combination with other simple sugars, fructose stimulates rapid fluid and solute absorption in the small intestine and helps increase exogenous carbohydrate oxidation during exercise, an important response for improving exercise performance. Although additional research is required to clarify the possible health-related implications of long-term intake of large amounts of dietary fructose among athletes, regular exercise training and consequent high daily energy expenditure may protect athletes from the negative metabolic responses associated with chronically high dietary fructose intake.
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PMID:Fructose, exercise, and health. 2062 44

The present review updates the current knowledge on the question of whether high fructose consumption is harmful or not and details new findings which further pushes this old debate. Due to large differences in its metabolic handling when compared to glucose, fructose was indeed suggested to be beneficial for the diet of diabetic patients. However its growing industrial use as a sweetener, especially in soft drinks, has focused attention on its potential harmfulness, possibly leading to dyslipidemia, obesity, insulin resistance/metabolic syndrome and even diabetes. Many new data have been generated over the last years, confirming the lipogenic effect of fructose as well as risks of vascular dysfunction and hypertension. Fructose exerts various direct effects in the liver, affecting both hepatocytes and Kupffer cells and resulting in non-alcoholic steatotic hepatitis, a well known precursor of the metabolic syndrome. Hepatic metabolic abnormalities underlie indirect peripheral metabolic and vascular disturbances, for which uric acid is possibly the culprit.Nevertheless major caveats exist (species, gender, source of fructose, study protocols) which are detailed in this review and presently prevent any firm conclusion. New studies taking into account these confounding factors should be undertaken in order to ascertain whether or not high fructose diet is harmful.
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PMID:Fructose and cardiometabolic disorders: the controversy will, and must, continue. 2066 32


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