Plasma cholesteryl ester transfer protein and lipoprotein levels during treatment of growth hormone-deficient adult humans.

The incidence of atherosclerosis is increased in growth hormone (GH) deficient-individuals. Nonetheless, the antiatherogenic benefits of GH replacement therapy remain uncertain. In this study the effect of human recombinant growth hormone (hrGH) replacement therapy administered to GH-deficient adults on the plasma cholesteryl ester transfer protein (CETP) concentration and activity was analyzed. These findings were related to changes in the concentrations of the plasma lipoproteins. The hrGH was administered for 12 mon to human GH-deficient patients (n = 13; 8 men, 5 women). During the study plasma lipoproteins were separated by ultracentrifugation, and plasma cholesterol esterification rate (CER), endogenous CETP activity, and CETP concentration were measured. GH replacement therapy transiently (at 3 mon) lowered plasma concentration of CETP and low density lipoprotein-cholesterol (LDL-C) and raised total triglycerides. Furthermore, hrGH permanently increased both the plasma lipoprotein(a) [Lp(a)] concentration, which is known as atherogenic, and the proportion of cholesteryl ester in the high density lipoprotein2 (HDL2) particles, which is potentially atheroprotective. The simultaneous decrease of the plasma CETP and LDL-C concentrations elicited by hrGH indicated a close relationship between LDL metabolism and the regulation of the CETP gene expression. Endogenous CETP activity and the CER were not modified because these parameters are regulated in opposite ways by plasma levels of triglycerides; that is, CER increased and CETP decreased.

Dietary medium-chain triacylglycerol prevents the postprandial rise of plasma triacylglycerols but induces hypercholesterolemia in primary hypertriglyceridemic subjects.

BACKGROUND: Previous studies showed divergent results concerning the influence of medium-chain triacylglycerol (MCT) on lipoprotein metabolism. OBJECTIVE: The objective of this study was to compare the effects of MCT and corn oil on plasma lipids in primary hypertriglyceridemic patients. DESIGN: Ten subjects ate different proportions of corn oil and MCT for 12 wk. The subjects first ate a low-fat diet for 2 wk and during the next 4 wk, corn oil was added as the sole source of fat. Thereafter, for 2-wk periods, the subjects were sequentially fed corn oil and MCT mixed in the following proportions: 3:1, 1:1, and 0:1. Fasting plasma total cholesterol, triacylglycerol, and HDL-cholesterol concentrations were measured at the end of each period. At the end of the 100%-corn oil and of the 100%-MCT periods, subjects were fed a test meal containing the respective oil (40 g fat/m(2) body surface area) and total cholesterol and triacylglycerols were measured at 2-h intervals over 8 h; fasting lipoprotein composition was also measured. RESULTS: Compared with corn oil, MCT was associated with a higher mean (+/-SD) fasting total cholesterol concentration (6.39 +/- 1.14 compared with 5.51 +/- 0.98 mmol/L, respectively; P < 0. 05); non-HDL-cholesterol concentrations were also higher with MCT (5. 36 +/- 1.11 mmol/L) than with corn oil (4.51 +/- 0.92 mmol/L; P < 0. 005). In response to the liquid test meal, plasma total cholesterol did not change with either diet but triacylglycerols increased with the 100%-corn oil diet. CONCLUSIONS: MCT prevents the risk of pancreatitis due to postprandial hypertriglyceridemia but has the inconvenience of raising total cholesterol concentrations in primary hypertriglyceridemic subjects.

Plasma cholesteryl ester transfer protein concentration, high-density lipoprotein cholesterol esterification and transfer rates to lighter density lipoproteins in the fasting state and after a test meal are similar in Type II diabetics and normal controls.

Rates of ester formation from [3H]cholesterol and of [3H]cholesteryl ester transfer from the HDL-containing plasma fraction to lipoproteins of lighter densities (apo B-containing LP) and plasma cholesteryl ester transfer protein concentration (CETP) were measured in normotriglyceridemic Type II diabetics (n = 11) and normal controls (n = 10) both in the fasting state and 4 h after a standard milk-shake test meal (50g of fat/m of body surface). The percent of [3H]cholesteryl ester synthesis was measured in a plasma [3H]cholesterol-HDL containing preparation incubated for 30 min and the [3H]cholesteryl ester transfer was measured upon precipitation of apo B-containing lipoproteins with dextran sulphate/MgCl2 following a 2 h period of plasma incubation with [3H]cholesteryl ester-HDL. The test meal significantly increased the plasma triglyceride concentration and to a similar extent in diabetics and in normal controls. Both a HDL-[3H]cholesteryl ester synthesis and transfer rates were equally stimulated in diabetics and in controls. When data were expressed by the concentration of plasma triglycerides, cholesteryl ester formation and transfer rates were similar in the alimentary and fasting periods, and when expressed per apo B concentration, cholesteryl ester transfer rates rose during the alimentary period in both diabetics and controls indicating that there was a net gain of cholesteryl ester per apo B lipoprotein. Plasma CETP mass, and neutral lipid transfer activity were similar in diabetics and normal controls demonstrating that the reverse transport of cholesterol through the apo B lipoprotein pathway is not altered in normotriglyceridemic Type II diabetics.

Plasma cholesteryl ester synthesis, cholesteryl ester transfer protein concentration and activity in hypercholesterolemic women: effects of the degree of saturation of dietary fatty acids in the fasting and postprandial states.

Hypercholesterolemic women (n = 19) sequentially maintained on a long-term saturated (SAT) or a polyunsaturated (PUFA) fatty acid-rich diet, respectively, were studied in the fasting state and after a meal rich in SAT or PUFA. When apo B-containing lipoprotein was excluded from plasma the in vitro HDL-14C-cholesterol esterification rate was identical for the saturated (SAT) and polyunsaturated (PUFA) fatty acid diets, and did not increase during the postprandial period. Rates of transfer of 14C-cholesteryl ester to apo B-containing lipoproteins from HDL were also similar for both diets in the fasting state and increased to the same extent in the postprandial period in parallel with the rise in plasma triglycerides. When transfer data were related to the plasma concentration of apo B, the gain of cholesteryl ester by the triglyceride-containing particles (VLDL + LDL) also increased in the postprandial period to a similar extent for both diets. Cholesteryl ester transfer protein (CETP) concentration measured by radioimmunoassay was similar during both experimental diets, although greater in the postprandial period for the PUFA diet. The rate limiting factor for CETP-mediated transfer of HDL-derived cholesteryl ester (CE) was the plasma triglyceride concentration, that is, the content of triglycerides per lipoprotein particle and the quantity of TG-containing particles (VLDL + LDL). In contrast, the fatty acid composition of these particles had less effect on CETP-mediated CE transfer.

Effect of dietary fish oil on the rate of very low density lipoprotein triacylglycerol formation and on the metabolism of chylomicrons.

The mechanism by which omega 3 fatty acids lower plasma triacylglycerol levels was investigated. Rats were fed fish oil, olive oil (10% fat by weight) or a nonpurified diet (4% fat by weight) for 15 days. Lipoprotein lipase was inhibited by intra-arterial administration of Triton WR 1339 to estimate hepatic triacylglycerol output. Rats fed the olive oil diet showed a higher rate of triacylglycerol formation than rats fed the omega 3 fatty acid diet or the low-fat diet. All three groups showed identical rates of removal from plasma of intraarterially administered artificial chylomicrons that had simultaneously been labeled with cholesteryl [1-14C]oleate and [9,10(n)-3H]triolein. Liver radioactivity and total fat content were lowest in rats fed the fish oil diet, indicating that omega 3 fatty acids were preferentially metabolized in liver. Chylomicrons obtained from donor rats fed either fish oil containing [14C]cholesterol or olive oil containing [3H]cholesterol were removed at similar rates when infused together intraarterially into recipient animals. A slower formation of plasma very low density lipoprotein triacylglycerols in rats fed fish oil is probably due to a faster rate of oxidation of the fatty acid chains in the liver resulting in decreased plasma triacylglycerol concentrations.