Studies on the Mechanism in Hyperlipidemia:Releasing Mechaoism of Very Low Density Lipoprotein (VLDL) of Rats and Relationship between High Density Lipoprotein and VLDL-Catabolism in Human Plasma

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Diet has a powerful effect on plasma lipid concentration, however these levels often vary among individual cases on the same diet. The present studies were undertaken to investigate the releasing mechanism of very low density lipoprotein (VLDL) in lanolin-induced hypercholesterolemia of rat and the role of high density lipoprotein (HDL) on catabolic pathway of VLDL in human plasma. Material and Methods; A) Three adult wister strain rats were loaded by 10g of lanolin (oral) before experiments. Four rats were remained fasting overnight as control. 15μCi/rat of 14C-1-palmitate and 50μCi of 3H-2-glycine were injected venously (at 3 hours after lanolin load on experimental group). At 1 hour after injection of these labeled compounds plasma lipoprotein fraction was separated by using the ultracentrifuge-method and lipid fraction of liver-lipid was separated by the thin layer chromatogram. Radioactivity of each lipid fraction and of lipoprotein-protein were counted by scintiration counter. B) Fifteen hospitarized subjects have consumed the formula diet (1000 Cal./day containing 140g of carbohydrate and 80g of protein) for four weeks. These subjects were selected by following criterion; Relative body weight after the diet therapy was less than 120%. Plasma triglyceride (TG) level after the diet therapy was less than 117g/100ml. The body weight was decreased by more than 2% after four weeks of the diet therapy. These hyperlipidemic subjects have been divided into two groups according to the response of low density lipoprotein (LDL) to the diet therapy. Before and after four weeks of the diet therapy blood sample was drown in the morning after overnight fasting. Lipoprotein fraction was separated by ultracentrifugation. Results and Discussion; A) Injected 14C-palmitate was mainly incorporated into phospholipids (PL) of liver in control group. During lanolin loading the incorporation of 14C-palmitate into hepatic fat was signif-icantly increased. The increased incorporation was caused by an increase in PL accompanied by an increase in incorporation of 3H-glycine into HDL-protein. Additionaly, incorporation of 14C-palmitate into VLDL-TG and also of 3H-glycine into VLDL-protein were significantly increased by lanolin load. Since PL has an important role of activation of lipoprotein lipase (LPL) which hydrolizes VLDL-TG in blood stream, the increased incorporation of 14C-palmitate into PL by lanolin load might be due inevitably to accelerate LPL. On the other hand, the increasing in hepatic PL was inhibited by CCl4-infusion which is well known that CCl4 could induce the secretion of VLDL from liver. This result was suggested that PL might play an important role for development in liver, especially releasing mechanism of connecting unpolar lipids with VLDL-protein. B) There are two type on the response of LDL-cholesterol to the diet therapy which diet factors were restricted. These types have not characteristic of serum lipids level. The group characterized by a decreased LDL-cholesterol has higher level of HDL-cholesterol than the group with an increased LDL-cholesterol. On the other hand, the group with an increased LDL-cholesterol has high ratio of LDL to HDL and of cholesterol to TG in VLDL. These results were suggested the enough HDL, as shown in the group with decreased LDL-cholesterol, made smoothly on catabolism of VLDL in plasma. We posturated from these results in rat and human that the accelerated release of VLDL might be the first step when several diet factors have been loaded. On the process of VLDL-release from liver PL might play the most important role to connect lipids synthesized in liver with apo-VLDL and there appears to be accompanied by an increase in HDL for facilitating VLDL-catabolism in plasma.
Japan Society of Clinical Chemistryの論文

Studies on the Mechanism in Hyperlipidemia:Releasing Mechaoism of Very Low Density Lipoprotein (VLDL) of Rats and Relationship between High Density Lipoprotein and VLDL-Catabolism in Human Plasma

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