Serum Very Low Density Lipoprotein Levels Research Articles

Impaired-Inactivation of FoxO1 Contributes to Glucose-Mediated Increases in Serum Very Low-Density Lipoprotein

For patients with diabetes, insulin resistance and hyperglycemia both contribute to increased serum triglyceride in the form of very low-density lipoprotein (VLDL). Our objective was to define the insulin conditions in which hyperglycemia promotes increased serum VLDL in vivo. We performed hyperglycemic-hyperinsulinemic clamp studies and hyperglycemic-hypoinsulinemic clamp studies in rats, with metabolic tracers for glucose flux and de novo fatty acid synthesis. When blood glucose was clamped at hyperglycemia (17 mm) for 2 h under hyperinsulinemic conditions (4 mU/kg . min), serum VLDL levels were not increased compared with baseline. We speculated that hyperinsulinemia minimized glucose-mediated VLDL changes and performed hyperglycemic-hypoinsulinemic clamp studies in which insulin was clamped near fasting levels with somatostatin (17 mm blood glucose, 0.25 mU/kg . min insulin). Under low-insulin conditions, serum VLDL levels were increased 4.7-fold after hyperglycemia, and forkhead box O1 (FoxO1) was not excluded from the nucleus of liver cells. We tested the extent that impaired inactivation of FoxO1 by insulin was sufficient for glucose to promote increased serum VLDL. We found that, when the ability of insulin to inactivate FoxO1 is blocked after adenoviral delivery of constitutively active FoxO1, glucose increased serum VLDL triglyceride when given both by ip glucose tolerance testing (3.5-fold increase) and by a hyperglycemic clamp (4.6-fold). Under both experimental conditions in which insulin signaling to FoxO1 was impaired, we found increased activation of carbohydrate response element binding protein. These data suggest that glucose more potently promotes increased serum VLDL when insulin action is impaired, with either low insulin levels or disrupted downstream signaling to the transcription factor FoxO1.

Hypotensive and lipid regulatory actions of 4‐hydroxyderricin, a chalcone from Angelica keiskei, in stroke‐prone spontaneously hypertensive rats

1. Previously, we found that Angelica keiskei extract (ethyl acetate extract from the yellow liquid of stems) elevated serum high-density lipoprotein (HDL) levels and reduced liver triglyceride content in stroke-prone spontaneously hypertensive rats (SHRSP). To identify the active substance in A. keiskei extract, we examined the effect of 4-hydroxyderricin, a characteristic chalcone isolated from the yellow liquid of stems, on blood pressure and lipid metabolism in SHRSP. 2. Six-week-old male SHRSP were fed diets containing 0.07% 4-hydroxyderricin for 7 weeks with free access to the diet and water. Elevation of systolic blood pressure was significantly suppressed after 7 weeks treatment. Serum very low-density lipoprotein (VLDL) levels were significantly reduced, without any effect on HDL levels, and were associated with a significant decrease in the serum concentration of free fatty acids. 3. In the liver, significant decreases in relative liver weight and triglyceride content were found after treatment with 4-hydroxyderricin for 7 weeks. 4. An investigation of hepatic mRNA expression of proteins involved in lipid metabolism indicated that a significant decrease in microsomal triglyceride transferprotein may be responsible for the decrease in serum VLDL levels and that significant decreases in adipocyte determination and differentiation factor 1 and fatty acid synthase may be responsible for the decrease in hepatic triglyceride content. 5. In conclusion, dietary 4-hydroxyderricin produces suppression of the elevation of systolic blood pressure, reduction of serum VLDL levels and a decrease in hepatic triglyceride content in SHRSP.

Lipoprotein concentrations in serum and in biopsy samples of arterial intima A quantitative comparison

Lipoprotein concentrations were compared in serum and in samples of arterial intima obtained during cardiovascular surgery. The interval between blood sampling and surgery did not exceed 48 hours. Apolipoproteins B and C, the major proteins of low density lipoprotein (LDL) and very low density lipoprotein (VLDL) respectively, were detectable by immuno-assay in all arterial specimens. Highly significant positive correlations existed between the levels of lipoproteins in the intima and in serum. In patients with elevated serum VLDL levels (Type IV hyperlipoproteinaemia) arterial concentrations of apolipoproteins B and C were increased about two-fold; in those with raised LDL levels in serum (Type II), with or without concomitant elevation of VLDL levels, the concentration of apolipoprotein B was increased almost 5-fold in the arterial intima. The arterial wall therefore contains lipoproteins or their immunologically-similar metabolites at concentrations which are determined in part by serum lipoprotein levels.