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K Cianflone

Publications and source records attributed to K Cianflone.

79 records · Page 5Linked to original sources

Metabolic response of Acylation Stimulating Protein to an oral fat load.

Acylation Stimulating Protein (ASP) is a small (mol wt 14,000), basic (pI 9.0) protein present in human plasma. When examined in vitro with normal human cultured skin fibroblasts and adipocytes, ASP appears to be the most potent stimulant of triglyceride synthesis yet described. In this study, a competitive ELISA assay for ASP has been developed using immunospecific polyclonal antibodies, and ASP levels have been measured in seven normal subjects. Following an oral fat load, a sustained significant increase in ASP occurs, whereas after an oral glucose load, ASP levels do not change significantly. These responses are entirely opposite to those of insulin, which rises sharply but transiently after an oral glucose load but is unchanged after an oral fat load. Both the fasting and peak ASP levels were significantly related to the postprandial lipemia. These data provide the first in vivo evidence that Acylation Stimulating Protein may play an important physiological role in the normal response to an oral fat load.

Adult↗

The effect of a plasma protein fraction on lipid synthesis in cultured skin fibroblasts from normals and patients with hyperapobetalipoproteinemia.

Lipid synthesis was measured in cultured skin fibroblasts obtained from normals and patients with Hyperapobetalipoproteinemia (HyperapoB). Using lipoprotein-deficient serum medium, triglyceride synthesis and cholesterol esterification were greater in normals than in HyperapoB due to differences in de novo synthesis, not to differences in re-esterification or to different rates of hydrolysis. When normal and HyperapoB cells were incubated in serum-free medium, however, lipid synthesis was the same. Serum was then fractionated chromatographically and a partially purified protein fraction shown to be responsible for the stimulatory effect in normals.

Adult↗

Stimulation of fatty acid uptake and triglyceride synthesis in human cultured skin fibroblasts and adipocytes by a serum protein.

Lipoprotein deficient serum has been shown to enhance lipid synthesis in cultured normal human skin fibroblasts incubated in the presence of oleate-albumin. The factor responsible is nondialyzable and trypsin sensitive. The stimulation is proportional to the concentration of lipoprotein deficient serum in the media and is present at all oleate concentrations and incubation times assayed. The protein has been partially purified by column chromatography to yield a Peak II fraction which stimulates triglyceride synthesis in both fibroblasts and isolated human adipocytes. The stimulation is dependent on the concentration of protein fraction and increases to an apparent saturation level of 200% in fibroblasts. Triglyceride synthesis, however, increases to a much greater extent in adipocytes and did not demonstrate saturation at the maximum Peak II protein concentration assayed. These results suggest that human serum contains a protein which stimulates fatty acid uptake and esterification by adipose tissue.

Adipose Tissue↗

Hyperapobetalipoproteinemia: the major dyslipoproteinemia in patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis.

In the present study, plasma cholesterol, triglyceride, low density lipoprotein (LDL)-cholesterol, high density lipoprotein (HDL)-cholesterol, and the major protein in LDL, apoB, were measured in 28 patients with chronic renal failure treated with hemodialysis and in 28 patients with chronic renal failure treated with chronic ambulatory peritoneal dialysis (CAPD). Elevated plasma triglycerides and reduced HDL cholesterol were frequent in both the hemodialysis and CAPD patients. However LDL levels were significantly higher in the CAPD patients as evident both by LDL cholesterol and LDL apoB. Even so, only one of the CAPD patients was hypercholesterolemic whereas 14 (or 50%) had hyperapobetalipoproteinemia (HyperapoB). Insulin-dependent diabetes was more frequent in the CAPD group but only 2 of the 9 insulin-dependent diabetics in this group had HyperapoB, and therefore, diabetes mellitus cannot account for the difference between the 2 groups. Thus HyperapoB appears to be a prevalent dyslipoproteinemia in CAPD patients and as such might be another factor which places CAPD patients at particularly increased risk of atherosclerosis.

Adult↗

Familial aggregation and early expression of hyperapobetalipoproteinemia.

Family history is an important predictor of coronary risk. However, this relation, in large part, is not explained by the known risk factors such as systemic hypertension or hyperlipidemia. In the present study, plasma lipid, lipoprotein lipid, and plasma low-density lipoprotein (LDL) apoB levels were measured in 66 offspring (myocardial infarction [MI] offspring) of 24 families in which an index parent had premature coronary artery disease and hyperapobetalipoproteinemia. These results were compared to those obtained in 207 control children and young adults. Univariate analysis revealed that plasma LDL apoB and all other lipid and lipoprotein levels except high-density lipoprotein cholesterol were significantly higher in the MI offspring. Multivariate analysis showed plasma LDL apoB and LDL cholesterol best differentiated the MI offspring from control children and young adults. Of the 66 children, 22 had hyperapobetalipoproteinemia, of whom only 7 had clearly abnormal LDL cholesterol or plasma triglyceride levels. Thus, a substantial portion of children born to a parent with premature coronary artery disease and hyperapobetalipoproteinemia have the same disorder of lipoprotein metabolism.

Adolescent↗

Hyperapobetalipoproteinemia. Plasma lipoprotein responses to oral fat load.

To better define lipid transport in patients with hyperapobetalipoproteinemia (HyperapoB), the response to an oral fat load was studied in six normotriglyceridemic patients with the disorder. Plasma triglycerides; Sf greater than 400, and Sf 20 to 400 triglycerides; Sf greater than 20 B100; total HDL and HDL subfractions (HDL2 and HDL3) were measured serially for a 7-hour period after an oral fat load and changes in these parameters were compared to those observed in six normolipidemic controls. In addition, plasma triglyceride levels and HDL2 and HDL3 cholesterol were also determined in seven patients with Type IV hyperlipoproteinemia: three with normal LDL apo B levels and four with HyperapoB. When the two normotriglyceridemic groups were compared, the patients with HyperapoB had significantly higher fasting levels of SF greater than 400 lipoproteins and higher fasting VLDL and LDL levels than the normal patients. After the fat load, Sf 20 to 400 triglycerides and Sf greater than 20 B100 levels increased in both groups. Plasma triglycerides rose to a higher level in the HyperapoB patients than in the normal group, but more strikingly, remained elevated in the HyperapoB patients, an elevation due principally to a persistant increase in Sf greater than 400 triglycerides. On the other hand, HDL2 cholesterol dropped substantially in the HyperapoB patients but not in the normal patients. Finally, in the hypertriglyceridemic group, after the fat load, HDL2 cholesterol levels did not change in the patients with normal LDL apo B levels but did decrease in those with elevated plasma LDL apo B.

Adult↗

In vitro interactions between low density lipoprotein from hyperapobetalipoproteinemic plasma and arterial wall proteoglycans.

OBJECTIVE: To examine the interactions of low density lipoprotein-B (LDL-B) with proteoglycans (PG) in vitro. DESIGN: The PG were isolated from human aortas, removed at autopsy by a combination of extraction with 4M guanidine-Tris buffer containing protease inhibitors and fractionation on a DEAE-Sephacel ion-exchange chromatography column. LDL and LDL-B from healthy or hyperapobetalipoproteinemic sera, respectively, were isolated by standard density flotation techniques followed by radioiodination. Radiolabelled lipoproteins (LP) were incubated with proteoglycans at 4 or 37 degrees C in a low ionic strength buffer with or without addition of polyethylene glycol (PEG) which was used to enhance precipitation of the resulting LP-PG complexes. MAIN RESULTS: Data revealed that a specific ratio of LP to PG is a prerequisite for optimal interactions between these macromolecules. Further, it was observed that LDL-B forms fewer precipitable complexes than normal LDL at 4 degrees C. However, at physiological temperature or with the addition of PEG, precipitation of the two LDLs was equal. CONCLUSION: LDL and LDL-B showed equal reactivity with PG in terms of precipitable complexes.

Aorta↗