Postprandial plasma lipoprotein changes in human subjects of different ages

Plasma lipoprotein changes were monitored for 12 hr after a fat-rich meal (1 g of fat/kg body weight) in 22 subjects (9 males, 13 females, 22-79 yr old). Plasma triglyceride, measured hourly, peaked once in some subjects, but twice or three times in others. The magnitude of postprandial triglyceridemia varied considerably between subjects (range: 650-4082 mg.hr/dl). Males tended to have greater postprandial triglyceridemia than females, and elderly subjects had significantly (P less than 0.05) greater postprandial triglyceridemia than younger subjects. Total plasma cholesterol, measured every three hr, increased significantly (6.0 +/- 2.1%) in 7 subjects, decreased significantly (7.1 +/- 1.2%) in 10 subjects, and remained unchanged in the remainder. Single spin ultracentrifugation and dextran sulfate precipitation procedures were used to quantitate triglyceride and cholesterol in triglyceride-rich lipoproteins (TRL, d less than 1.006 g/ml), low density lipoproteins (LDL), and high density lipoproteins (HDL). Plasma TRL and HDL triglyceride increased after the fat meal, while LDL triglyceride decreased at 3 hr but increased at 9 and 12 hr. TRL cholesterol increased postprandially, while LDL and HDL cholesterol decreased. Phospholipid (PL), free (FC) and esterified (EC) cholesterol measurements were carried out on the plasma and lipoprotein fractions of 8 subjects. Plasma PL increased significantly at 3, 6, and 9 hr after the fat-rich meal, due to increases in TRL and HDL PL. TRL CE increased postprandially, but a greater decrease in LDL and HDL CE caused plasma CE to be decreased. Plasma FC increased, predominantly due to an increase in TRL FC. Plasma concentrations of apolipoprotein A-I and apolipoprotein B both decreased after the fat-rich meal. The magnitude of postprandial triglyceridemia was inversely correlated with HDL cholesterol levels (r = -0.502, P less than 0.05) and positively correlated with age (r = -0.449, P less than 0.05), fasting levels of plasma triglyceride (r = 0.636, P less than 0.01), plasma apoB (r = 0.510, P less than 0.05), TRL triglyceride (r = 0.564, P less than 0.01), TRL cholesterol (r = 0.480, P less than 0.05) and LDL triglyceride (r = 0.566, P less than 0.01). Change in postprandial cholesterolemia was inversely correlated with fasting levels of HDL cholesterol (r = -0.451, P less than 0.05) and plasma apoA-I (r = -0.436, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)     

Lipid metabolism in endotoxic rats: decrease in hepatic triglyceride lipase activity

Studies were conducted to investigate the effect of E. coli endotoxin administration on hepatic triglyceride lipase (H-TGL) activity in rats, since H-TGL activity is known to behave differently from lipoprotein lipase (LPL) activity in various situations. Plasma triglyceride and free fatty acid concentrations were markedly elevated in animals after injection of endotoxin. Cholesterol and phospholipids were also increased significantly. Lipoprotein analysis by ultracentrifugation showed that the most pronounced increase of lipoproteins was in the VLDL and IDL fractions. Triglyceride lipase activities in post-heparin plasma were markedly decreased. A selective assay for H-TGL activity using a specific antibody revealed that this enzyme as well as LPL is significantly decreased (26% of control) in endotoxic animals. Thus, the increase of VLDL and IDL appears to result from the decrease of both of LPL and H-TGL.     

Postheparin plasma lipoprotein and hepatic lipase are determinants of hypo- and hyperalphalipoproteinemia

To study the role of the two postheparin plasma lipolytic enzymes, lipoprotein lipase (LPL) and hepatic lipase (HL) in high density lipoprotein (HDL) metabolism at a population level, we determined serum lipoproteins, apoproteins A-I, A-II, B, and E, and postheparin plasma LPL and HL activities in 65 subjects with a mean HDL-cholesterol of 34 mg/dl and in 62 subjects with a mean HDL-cholesterol of 87 mg/dl. These two groups represented the highest and lowest 1.4 percentile of a random sample consisting 4,970 subjects. The variation in HDL level was due to a 4.1-fold difference in the HDL2 cholesterol (P less than 0.001) whereas the HDL3 cholesterol level was increased only by 32% (P less than 0.001) in the group with high HDL-cholesterol. Serum apoA-levels were 128 +/- 2.2 mg/dl and 210 +/- 2.8 mg/dl (mean +/- SEM) in hypo- and hyper-HDL cholesterolemia, respectively. Serum apoA-II concentration was elevated by 28% (P less than 0.001) in hyperalphalipoproteinemia. The apoA-I/A-II ratio was elevated only in women with high HDL-cholesterol but not in men, suggesting that elevation of apoA-I is involved in hyperalphalipoproteinemia in females, whereas both apoA proteins are elevated in men with high HDL cholesterol. Serum concentration of apoE and its phenotype distribution were similar in the two groups. The HL activity was reduced in the high HDL-cholesterol group (21.2 +/- 1.5 vs. 38.5 +/- 1.8 mumol/h/ml, P less than 0.001), whereas the LPL activity was elevated in the group with high HDL-cholesterol compared to subjects with low HDL-cholesterol (27.8 +/- 1.3 vs. 19.9 +/- 0.8 mumol/h/ml, P less than 0.001). The HL and LPL activities correlated in opposing ways with the HDL2 cholesterol (r = 0.57, P less than 0.001 and r = 0.51, P less than 0.001, respectively), and this appeared to be independent of the relative ponderosity by multiple correlation analysis. The results demonstrate major influence of both HL and LPL on serum HDL cholesterol concentration at a population level.     

Reduction in the concentration and activity of plasma cholesteryl ester transfer protein by alcohol.

Plasma cholesteryl esters, synthesized within high density lipoproteins (HDL), may be transferred from HDL particles to other lipoproteins by plasma cholesteryl ester transfer protein (CETP). Alcohol consumption is associated with increased HDL cholesterol concentration and reduced plasma CETP activity. The alcohol-induced decrease in CETP activity may be due to a low concentration of CETP in plasma or the inhibition of CETP by specific inhibitor proteins or alterations in the composition of plasma lipoproteins. The first two possibilities are studied further in this paper using data on 47 alcohol abusers and 31 control subjects. The activity of CETP was measured as the rate of cholesteryl ester transfer between radio-labeled low density lipoproteins and unlabeled HDL using an in vitro method independent of endogenous plasma lipoproteins. Plasma CETP concentration was determined by a Triton-based radioimmunoassay. The alcohol abusers consuming alcohol (on average 154 g/day) had 28% higher HDL cholesterol (P less than 0.01), 27% lower plasma CETP concentration (P less than 0.001), and 22% lower plasma CETP activity (P less than 0.001) than the controls. Plasma CETP concentration showed a negative correlation with HDL cholesterol among all the subjects (r = -0.317, P less than 0.01) but not among the alcohol abusers alone (r = -0.102, N. S.). During 2 weeks of alcohol withdrawal, plasma CETP concentration and activity of 8 subjects increased, whereas HDL cholesterol decreased by 42% (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance

Plasma phospholipid transfer protein (PLTP) is thought to play a major role in the facilitated transfer of phospholipids between lipoproteins and in the modulation of high density lipoprotein (HDL) particle size and composition. However, little has been reported concerning the relationships of PLTP with plasma lipoprotein parameters, lipolytic enzymes, body fat distribution, insulin, and glucose in normolipidemic individuals, particularly females. In the present study, 50 normolipidemic healthy premenopausal females were investigated. The relationships between the plasma PLTP activity and selected variables were assessed. PLTP activity was significantly and positively correlated with low density lipoprotein (LDL) cholesterol (r(s) = 0.53), apoB (r(s) = 0.44), glucose (r(s) = 0.40), HDL cholesterol (r(s) = 0.38), HDL(3) cholesterol (r(s) = 0.37), lipoprotein lipase activity (r(s) = 0.36), insulin (r(s) = 0.33), subcutaneous abdominal fat (r(s) = 0.36), intra-abdominal fat (r(s) = 0.29), and body mass index (r(s) = 0.29). HDL(2) cholesterol, triglyceride, and hepatic lipase were not significantly related to PLTP activity. As HDL(2) can be decreased by hepatic lipase and hepatic lipase is increased in obesity with increasing intra-abdominal fat, the participants were divided into sub-groups of non-obese (n = 35) and obese (n = 15) individuals and the correlation of PLTP with HDL(2) cholesterol was re-examined. In the non-obese subjects, HDL(2) cholesterol was found to be significantly and positively related to PLTP activity (r(s) = 0.44). Adjustment of the HDL(2) values for the effect of hepatic lipase activity resulted in a significant positive correlation between PLTP and HDL(2) (r(s) = 0.41), indicating that the strength of the relationship between PLTP activity and HDL(2) can be reduced by the opposing effect of hepatic lipase on HDL(2) concentrations. We conclude that PLTP-facilitated lipid transfer activity is related to HDL and LDL metabolism, as well as lipoprotein lipase activity, adiposity, and insulin resistance.     

Hydrogenated fat consumption affects acylation-stimulating protein levels and cholesterol esterification rates in moderately hypercholesterolemic women.

To determine whether hydrogenated fat consumption alters triglyceride metabolism and cholesterol esterification rates, 14 women (65-71 years of age) were provided with each of four diets for 5-week periods according to a randomized cross-over design. The experimental diets contained either soybean oil (SO), low trans squeeze (SQM), medium trans tub (TM), or high trans stick (SM) margarines. Triglyceride uptake by adipose tissue was determined by measuring plasma acylation-stimulating protein (ASP), FFA, glucose, and insulin levels, while rates of transfer and esterification rate of newly synthesized cholesterol (ER) were derived by using plasma CETP levels and the deuterium incorporation methodology. Plasma ASP levels were lowest (P < 0.05) in subjects on the SM diet (33.4 +/- 12.7 nM) compared with the SO (48.7 +/- 17.0 nM) and SQM (50.7 +/- 15.7 nM) diets. Conversely, FFA were highest (P < 0.05) on the SM diet (0.86 +/- 0.45 mM) relative to all the other diets. No differences were observed in plasma glucose and insulin levels among diets. A trend toward higher CETP levels after consumption of the SM diet was observed. However, the ER was lowest (P < 0.05) after the SM (0.111 +/- 0.062 g x day(-1)) diet and highest after consumption of the SQM (0.216 +/- 0.123 g x day(-1)) diet. In addition, ASP levels were negatively correlated with FFA (r = -0.63, P < 0.05), LDL cholesterol (r = -0.56, P < 0.05), and TG (r = -0.41, P < 0.05), whereas FFA was positively correlated with apolipoprotein B-containing lipoproteins (r = 0.58 and 0.47, for VLDL and LDL cholesterol, P < 0.05), and negatively correlated with HDL cholesterol (r = -0.51, P < 0.05). The ER was found to positively correlate with HDL cholesterol and HDL2 subfraction (r = 0.53 and 0.45, respectively, P < 0.05). Taken together, these data demonstrate that the alterations in circulating lipid levels, commonly observed with consumption of hydrogenated fat-rich diets, can be explained in part by changes in ASP activity as well as newly synthesized cholesterol ER.     

Comparison of gradient gel electrophoresis and zonal ultracentrifugation for quantitation of high density lipoproteins

The study was conducted to compare gradient gel electrophoresis (GGE) and zonal ultracentrifugation for quantitation of human plasma high density lipoproteins (HDL). Plasma samples were obtained from seven normal subjects consuming a high fat diet (65% total calories) followed by a high carbohydrate diet (65% total calories). HDL were fractionated into HDL2 and HDL3 by zonal ultracentrifugation and lipid and protein mass were determined. HDL were also fractionated by GGE and the results were compared to the zonal method. Zonally isolated HDL2 represented a homogeneous particle population that was equivalent to HDL2b as determined by GGE. By the zonal method, HDL2 accounted for 27 +/- 4% (mean +/- SEM) of total HDL mass in subjects on the high fat diet as compared to 16 +/- 2% in subjects fed the high carbohydrate diet; by GGE, the HDL2b values were 27 +/- 4% and 14 +/- 1%, respectively. The coefficient of correlation (n = 25) for the two methods was 0.894 (P less than 0.001).     

Effect of dietary palm oil on lipoprotein lipases: lipoprotein levels and tissue lipids in rat

The aims of our study were to investigate the effect of dietary palm oil on the levels of lipoprotein lipase, hepatic lipase, fat distribution (in the aorta and liver), and total cholesterol, HDL, LDL, and triacylglycerol levels in young rats (70 g body wt) over a period of 10 weeks. Palm oil-fed rats showed higher growth rate and lower triacylglycerol levels than the control group. Hepatic lipase activity was correlated to the liver fat distribution (correlation coefficient, r = +0.682) as seen by histopathological sections and was similar for both the palm oil and the control diets. Palm oil-fed rats exhibited a significantly higher HDL cholesterol to total plasma cholesterol ratio when compared to animals fed the control diet. The triacylglycerol levels correlated inversely to the HDL cholesterol levels (r = -0.536) while the lipoprotein lipase (LPL) activity correlated directly to the LDL level (r = +0.617) for both groups of animals. The fatty acid profiles of adipose and liver tissues and plasma revealed that saturated fatty acids--palmitic and stearic--were preferentially incorporated in liver and adipose tissues and less in the plasma. This accounts for lack of deposition in the arterial wall and for the antithrombotic tendency of palm oil. Thus, our present findings suggest that dietary palm oil may not contribute to the risk for coronary heart disease.     

Role of soy isoflavones in the hypotriglyceridemic effect of soy protein in the rat

The present study was undertaken to determine whether isoflavones present in soy protein isolate contribute to the triglyceride-lowering effect of the protein relative to casein. Plasma triglyceride concentrations, their secretion rate into blood circulation, and post-heparin plasma lipoprotein lipase activity (a major determinant of intravascular catabolism of triglycerides) were measured in the fasted state in male Sprague-Dawley rats fed for 21 days one of three experimental diets varying in protein source (20% weight/weight): soy protein isolate, casein or casein to which 1.82 mg/g isoflavones (genistein and daidzein) were added to match the isoflavone content of soy protein isolate. Body weight gain was slightly lower in soy protein fed rats than in casein fed rats, but this effect was not statistically significant (P = 0.22). Casein plus isoflavones diet induced intermediary weight gain. A decrease in plasma total triglycerides was observed in rats fed soy protein and casein plus isoflavones compared with casein (P < 0.05), and there was a tendency to a positive correlation between weight gain and plasma triglyceride concentrations (r = 0.35, P = 0.06). However, no significant effect was observed on hepatic triglyceride concentrations, triglyceride secretion rate by the liver and post-heparin plasma lipoprotein lipase activity. These results show that soy protein isolate, in comparison with casein, has a hypotriglyceridemic effect in the rat and suggest that isoflavones may be responsible, at least in part, for this effect. The lowering effect of soy protein isolate and isoflavones on plasma triglyceride concentrations may be mediated by an alteration in energy balance, and possibly by the hepatic production of lipoproteins more susceptible to intravascular hydrolysis. Subtle but sustained changes in triglyceride secretion and post-heparin plasma lipoprotein lipase activity may also be implicated.     

The apo E/apo CIII molar ratio affects removal of cholesterol ester from modified human lipoproteins injected into cebus monkeys

The removal of postprandial (PP) and postabsorptive (PA) human LDL and HDL cholesterol was examined in cebus monkeys (Cebus albifrons) following in vitro labelling of these lipoproteins by 3H-cholesterol in the presence or absence of DTNB. The removal of LDL cholesteryl ester was 3.5 and 2 times greater than that of HDL in male and female monkeys, respectively. Incubation with DTNB reduced cholesteryl ester removal by 45 and 52% for LDL and HDL, respectively. Cholesteryl ester from PA lipoproteins was removed 80% faster than that PP particles only when plasma was incubated without DTNB. Cholesterol removal from these lipoproteins was positively (r = 0.941) and significantly (P less than 0.001) correlated with the molar apo E/apo CIII ratio. The data suggest that density of lipoproteins was less important than their apoprotein composition in dictating their removal from circulation.     

Endogenously produced endothelial lipase enhances binding and cellular processing of plasma lipoproteins via heparan sulfate proteoglycan-mediated pathway

Endothelial lipase (EL) is a new member of the triglyceride lipase gene family, which includes lipoprotein lipase (LpL) and hepatic lipase (HL). Enzymatic activity of EL has been studied before. Here we characterized the ability of EL to bridge lipoproteins to the cell surface. Expression of EL in wild-type Chinese hamster ovary (CHO)-K1 but not in heparan sulfate proteoglycan (HSPG)-deficient CHO-677 cells resulted in 3-4.4-fold increases of 125I-low density lipoprotein (LDL) and 125I-high density lipoprotein 3 binding (HDL3). Inhibition of proteoglycan sulfation by sodium chlorate or incubation of cells with labeled lipoproteins in the presence of heparin (100 microg/ml) abolished bridging effects of EL. An enzymatically inactive EL, EL-S149A, was equally effective in facilitating lipoprotein bridging as native EL. Processing of LDL and HDL differed notably after initial binding via EL to the cell surface. More than 90% of the surface-bound 125I-LDL was destined for internalization and degradation, whereas about 70% of the surface-bound 125I-HDL3 was released back into the medium. These differences were significantly attenuated after HDL clustering was promoted using antibody against apolipoprotein A-I. At equal protein concentration of added lipoproteins the ratio of HDL3 to VLDL bridging via EL was 0.092 compared with 0.174 via HL and 0.002 via LpL. In summary, EL mediates binding and uptake of plasma lipoproteins via a process that is independent of its enzymatic activity, requires cellular heparan sulfate proteoglycans, and is regulated by ligand clustering.     

Human hepatoma (HepG2) cells secrete a single 65 K dalton triglyceride lipase immunologically identical to postheparin plasma hepatic lipase

A triacylglycerol lipase was isolated from the culture medium of HepG2 human hepatoma cells and its properties were compared to hepatic triglyceride lipase (H-TGL) from human postheparin plasma. The HepG2 cell enzyme bound to heparin-Sepharose, was eluted with 1 M NaCl and was not inhibited by 1 M salt. Western-blotting of the fractions from the heparin-Sepharose column with a monoclonal antibody prepared against postheparin plasma H-TGL and which binds to an epitope in the carboxyl-terminus of H-TGL gave a single immunoreactive protein band of 65 kDa. This finding of immunochemical identity was confirmed with polyclonal antibodies prepared against synthetic peptides of H-TGL corresponding to amino acid residues 82-94 near the amino-terminus and residues 468-477, the carboxyl-terminus of the enzyme. We conclude that HepG2 cells secrete a single triacylglycerol lipase with molecular weight properties and immunological characteristics identical to post-heparin plasma H-TGL.     

Differential response to low-fat diet between low and normal HDL-cholesterol subjects

Heart attacks frequently occur in normolipidemic subjects with low concentration of high density lipoproteins (35 mg/dL). We hypothesized that as subjects with low HDL-C already have low HDL concentrations, the major decrease of HDL-C will occur in subjects with normal HDL-C when a low-fat diet is consumed. Normolipidemic male subjects consumed three diets differing in total fat and saturated fat composition (AAD: 37%, Step-1: 28%, Step-2: 24% total fat) for 6 weeks in a three-period double-blind randomized crossover design. Plasma lipids and apolipoproteins were determined and changes in distribution of HDL subpopulations were evaluated. As a result of a low-fat diet, low HDL-C individuals slightly decreased their HDL-C, but substantially decreased their LDL-C resulting in a significant improvement in the LDL-C/HDL-C ratio. However, subjects with normal HDL-C levels decreased both their LDL-C and HDL-C resulting in an unchanged LDL-C/HDL-C ratio. We also observed significant differences in response to low-fat diets in HDL-C and alpha(1) concentrations between low and normal HDL-C subjects. In the normal HDL-C group, consumption of a low-fat diet also resulted in redistribution of apoA-I-containing HDL subpopulations, indicated by a decrease in the large apoA-I-only alpha(1) subpopulation. These data demonstrate that male subjects with low HDL-C respond to a low-fat diet differently than individuals with normal HDL-C.     

Studies on the mechanism of hypertriglyceridemia in Tangier disease. Determination of plasma lipolytic activities, k1 values and apolipoprotein composition of the major lipoprotein density classes

Mechanisms responsible for hypertriglyceridemia in Tangier disease were elucidated by an analysis of the plasma post-heparin lipolytic activities and the structural and metabolic properties of very low (VLDL) and low (LDL) density lipoproteins. The levels of lipoprotein lipase activity in six Tangier patients were significantly lower (P less than 0.001) than in 40 control subjects (8.1 +/- 3.3 (+/- S.D.) vs. 14.1 +/- 3.7 units/ml). In contrast, the levels of hepatic triacylglycerol lipase were higher (P less than 0.01) than in normal controls (14.4 +/- 3.9 vs. 9.3 +/- 4.0 units/ml). Because kinetic parameters such as Km or Vmax cannot be obtained with naturally occurring triacylglycerol-rich lipoproteins, the pseudo-first-order rate constant (k1) of triacylglycerol hydrolysis was used to assess the effectiveness of triacylglycerol-rich lipoproteins as substrates for lipoprotein lipase. The k1 values for Tangier VLDL (k1 = 0.017 +/- 0.002 min-1) were significantly lower (P less than 0.001) than the k1 values (0.036 +/- 0.008 min-1) for control VLDL. Both the Tangier and control LDL2 are similar in their resistance to the action of lipoprotein lipase, as shown by their low k1 values (0.002 +/- 0.001 and 0.001 +/- 0.001 min-1, respectively). The major compositional difference between the lipoproteins of Tangier disease and normal subjects was a significant increase in the percent content of apolipoprotein A-II in all lipoprotein particles with d less than 1.063 g/ml, with the greatest increase occurring in VLDL and the lowest in LDL2. These results were interpreted as indicating that, in Tangier disease, there is a lower reactivity of VLDL with lipoprotein lipase which may in part be attributed to the abnormal apolipoprotein composition. This finding, in conjunction with the reduced levels of lipoprotein lipase activity, may explain the hypertriglyceridemia in Tangier disease.     

Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography

We examined the association between rate of cholesterol esterification in plasma depleted of apolipoprotein B-containing lipoproteins (FER(HDL)), atherogenic index of plasma (AIP) [(log (TG/HDL-C)], concentrations, and size of lipoproteins and changes in coronary artery stenosis in participants in the HDL-Atherosclerosis Treatment Study. A total of 160 patients was treated with simvastatin (S), niacin (N), antioxidants (A) and placebo (P) in four regimens. FER(HDL) was measured using a radioassay; the size and concentration of lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. The S+N and S+N+A therapy decreased AIP and FER(HDL), reduced total VLDL (mostly the large and medium size particles), decreased total LDL particles (mostly the small size), and increased total HDL particles (mostly the large size). FER(HDL) and AIP correlated negatively with particle sizes of HDL and LDL, positively with VLDL particle size, and closely with each other (r = 0.729). Changes in the proportions of small and large lipoprotein particles, which were reflected by FER(HDL) and AIP, corresponded with findings on coronary angiography. Logistic regression analysis of the changes in the coronary stenosis showed that probability of progression was best explained by FER(HDL) (P = 0.005). FER(HDL) and AIP reflect the actual composition of the lipoprotein spectrum and thus predict both the cardiovascular risk and effectiveness of therapy. AIP is already available for use in clinical practice as it can be readily calculated from the routine lipid profile.     

Lipoprotein lipase activity and its relationship to high milk fat transfer during lactation in grey seals

Lipoprotein lipase regulates the hydrolysis of circulating triglyceride and the uptake of fatty acids by most tissues, including the mammary gland and adipose tissue. Thus, lipoprotein lipase is critical for the uptake and secretion of the long-chain fatty acids in milk and for the assimilation of a high-fat milk diet by suckling young. In the lactating female, lipoprotein lipase appears to be regulated such that levels in adipose tissue are almost completely depressed while those in the mammary gland are high. Thus, circulating fatty acids are directed to the mammary gland for milk fat production. Phocid seals serve as excellent models in the study of lipoprotein lipase and fat transfer during lactation because mothers may fast completely while secreting large quantities of high fat milks and pups deposit large amounts of fat as blubber. We measured pup body composition and milk fat intake by isotope (deuterium oxide) dilution and plasma post-heparin lipoprotein lipase activity in six grey seal (Halichoerus grypus) mother-pup pairs at birth and again late in the 16-day laction period. Maternal post-heparin lipoprotein lipase activity increased by an average of four-fold by late lactation (P=0.027), which paralleled an increase in milk fat concentration (from 38 to 56%; P=0.043). Increasing lipoprotein lipase activity was correlated with increasing milk fat output (1.3–2.1 kg fat per day) over lactation (P=0.019). Maternal plasma triglyceride (during fasting) was inversely correlated to lipoprotein lipase activity (P=0.027) and may be associated with the direct incorporation of longchain fatty acids from blubber into milk. In pups, post-heparin lipoprotein lipase activity was already high at birth and increased as total body fat content (P=0.028) and the ratio of body fat: protein incrased (P=0.036) during lactation. Although pup plasma triglyceride increased with increasing daily milk fat intake (P=0.023), pups effectively cleared lipid from the circulation and deposited 70% of milk fat consumed throughout lactation. Lipoprotein lipase may play an important role in the mechanisms involved with the extraordinary rates of fat transfer in phocid seals.Abbreviations FFA free fatty acid - HL hepatic lipase - LPL lipoprotein lipase - PH-HL post-heparin hepatic lipase - PH-LPL post-heparin lipoprotein lipase - VLDL very low density lipoprotein     

Enhanced cholesteryl ester transfer protein activities and abnormalities of high density lipoproteins in familial hypercholesterolemia.

Cholesteryl ester transfer protein may play a role in the cholesteryl ester metabolism between high density lipoproteins (HDL) and apolipoprotein B-containing lipoproteins. To investigate relationship between HDL and cholesteryl ester transfer protein (CETP) activity in the development of atherosclerosis, the present study has focused on CETP activity in the patients with familial hypercholesterolemia (GH). HDL-C and HDL-C/apo A-I mass ratio in heterozygous FH were lower than those in normolipidemic controls. There was a 2-fold increase in total CETP activity in incubated FH serum compared with normolipidemic controls. Assays for CETP activity in the lipoprotein deficient serum (d greater than 1.215 g/ml) were carried out by measuring the transfer of radioactive cholesteryl ester from HDL (1.125 less than d less than 1.21 g/ml) to LDL (1.019 less than d less than 1.060 g/ml). CETP activities in heterozygous FH (79 +/- 4 nmol/ml/h) was significantly higher than those in normolipidemic controls (54 +/- 6 nmol/ml/h). The increased total cholesteryl ester transfer mainly results from increased CETP activity in the d greater than 1.215 g/ml, possibly reflecting an increase in CETP mass in serum. Increased CETP activity in the d greater than 1.215 g/ml was correlated positively with IDL-cholesterol/triglyceride mass ratio (r = 0.496, p less than 0.01), and negatively with HDL-cholesterol/apo A-I mass ratio (r = -0.334, p less than 0.05). These results indicate that the enhanced CETP activities may contribute to increase risk for developing atherosclerosis in FH by changing the distribution of cholesteryl ester in serum lipoproteins.     

The Effects of Macronutrient Intake on Total and High‐molecular Weight Adiponectin: Results From the OMNI‐Heart Trial

Higher levels of the adipocyte‐specific hormone adiponectin have been linked to increased high‐density lipoprotein (HDL) and lower insulin resistance. This study was conducted to determine the influence of macronutrient intake on adiponectin levels. One hundred and sixty‐four pre‐ and stage‐1 hypertensive adults participated in the Optimal Macro‐Nutrient Intake Heart (OMNI‐Heart) trial, a crossover feeding study originally testing the effects of macronutrients on blood pressure. Participants underwent three 6‐week feeding periods: one rich in carbohydrates (CARB), one rich in monounsaturated fat (MUFA), and one rich in protein (PROT), while maintaining body weight. Their median plasma high molecular weight (HMW) and total adiponectin levels were 2.3 and 8.2 µg/ml, respectively, resulting in an average of 27% HMW adiponectin. Both HMW and total adiponectin levels decreased after baseline while the percent HMW adiponectin remained unchanged. Between diets, the MUFA diet maintained a higher level of both HMW and total adiponectin levels than either the CARB (HMW: +6.8%, P = 0.02; total: +4.5%, P = 0.001) or PROT (HMW: +8.4%, P = 0.003; total: +5.6%, P < 0.001) diets. Changes in total adiponectin levels were positively correlated to changes in HDL cholesterol irrespective of diets (Spearman r = 0.22–0.40). No correlation was found between changes in lipids, blood pressure, or insulin resistance by the homeostasis model assessment (HOMAIR). Macronutrient intake has effects on HMW and total adiponectin levels independent of weight loss. A diet rich in MUFA was associated with higher levels of total and HMW adiponectin in comparison to a carbohydrate‐ or protein‐rich diet. Effects seen in adiponectin paralleled those found with HDL cholesterol.     

Hepatic lipase gene -514C>T variant is associated with exercise training-induced changes in VLDL and HDL by lipoprotein lipase

Our objective was to test the hypothesis that a common polymorphism in the hepatic lipase (HL) gene (LIPC -514C>T, rs1800588) influences aerobic exercise training-induced changes in TG, very-low-density lipoprotein (VLDL), and high-density lipoprotein (HDL) through genotype-specific increases in lipoprotein lipase (LPL) activity and that sex may affect these responses. Seventy-six sedentary overweight to obese men and women aged 50-75 yr at risk for coronary heart disease (CHD) underwent a 24-wk prospective study of the LIPC -514 genotype-specific effects of exercise training on lipoproteins measured enzymatically and by nuclear magnetic resonance, postheparin LPL and HL activities, body composition by dual energy x-ray absorptiometry and computer tomography scan, and aerobic capacity. CT genotype subjects had higher baseline total cholesterol, HDL-C, HDL(2)-C, large HDL, HDL particle size, and large LDL than CC homozygotes. Exercise training elicited genotype-specific decreases in VLDL-TG (-22 vs. +7%; P < 0.05; CC vs. CT, respectively), total VLDL and medium VLDL, and increases in HDL-C (7 vs. 4%; P < 0.03) and HDL(3)-C with significant genotype×sex interactions for the changes in HDL-C and HDL(3)-C (P values = 0.01-0.02). There were also genotype-specific changes in LPL (+23 vs. -6%; P < 0.05) and HL (+7 vs. -24%; P < 0.01) activities, with LPL increasing only in CC subjects (P < 0.006) and HL decreasing only in CT subjects (P < 0.007). Reductions in TG, VLDL-TG, large VLDL, and medium VLDL and increases in HDL(3)-C and small HDL particles correlated significantly with changes in LPL, but not HL, activity only in CC subjects. This suggests that the LIPC -514C>T variant significantly affects training-induced anti-atherogenic changes in VLDL-TG, VLDL particles, and HDL through an association with increased LPL activity in CC subjects, which could guide therapeutic strategies to reduce CHD risk.     

Plasma lipids in Turkish children: impact of puberty, socioeconomic status, and nutrition on plasma cholesterol and HDL.

In Turkish adults, HDL cholesterol (HDL-C) levels are 10-15 mg/dl lower than those of adults in western Europe and the United States. In this study, we determined whether HDL-C levels in Turks are low from birth to adulthood and assessed the effect of socioeconomic status (SES) on plasma lipids and lipoproteins. Analyses of cord blood from 105 Turkish newborns showed low levels of plasma cholesterol ( approximately 60 mg/dl) and HDL-C (approximately 30 mg/dl), consistent with results from other Western ethnic groups. Prepubescent 8- to 10-year-old Turkish boys and girls of upper (n = 82) and lower (n = 143) SES had high HDL-C levels (50-60 mg/dl) similar to those of western European children. However, the cholesterol (154-158 mg/dl) and HDL-C (55-58 mg/dl) levels of upper SES children were approximately 25 and approximately 12 mg/dl higher, respectively, than those of lower SES children. Height, weight, skinfold thickness, and estimated body fat were greater in the upper SES children and appeared to reflect dietary differences. Upper SES children consumed more total fat (approximately 35% vs. 25% of total calories), including more saturated fat of animal origin, and less carbohydrate (approximately 50% vs. 62% of total calories), consistent with their elevated plasma cholesterol levels. Carbohydrate intake correlated inversely with the HDL-C level. The HDL-C levels in the prepubescent children, especially those of higher SES, who consumed diets more like western Europeans, decreased markedly to adult levels, with males exhibiting a approximately 20 mg/dl decrease (from 58 to 37 mg/dl) and females a approximately 13 mg/dl decrease (from 55 to 42 mg/dl). SES did not affect HDL-C levels in adults. The profound decrease may reflect alterations in androgen/estrogen balance in Turks at puberty and a modulation of hepatic lipase affecting HDL-C levels.