Effects of ingestion of thermally oxidized edible oils on plasma lipids, lipoproteins and postheparin lipolytic activity of rats

Acute (after 4 hr) and short-term (after 7 days) effects of ingesting heated and unheated groundnut, coconut and safflower oils on plasma lipids, lipoproteins and postheparin lipopolytic activity (PHLA) were studied in rats. All heated oils were characterized by increases in carbonyl value, peroxide value and free fatty acid (FFA) content, except heated coconut oil which showed a decrease in FFA content. Heating procedure also did not alter to an appreciable extent their fatty acid compositions. Acute and short-term effects of feeding heated and unheated oils showed no significant differences in rat plasma levels of total cholesterol (TC), total triglycerides, total phospholipids, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol + very-low-density lipoprotein cholesterol, TC/HDL-C ratio and PHLA. Inspite of certain changes in some of the indices of thermal alteration of these heated oils, consumption of such heated oils by rats did not have any significant effect on various plasma parameters in these animals.     

Influence of cholesterol status on blood lipid and lipoprotein enzyme responses to aerobic exercise.

To compare postexercise changes in plasma lipids and lipoprotein enzymes in 13 hypercholesterolemic (HC) and 12 normocholesterolemic men [total cholesterol (TC) 252 +/- 5 vs. 179 +/- 5 mg/dl], fasting blood samples were obtained 24 h before, immediately, 24, and 48 h after a single bout of treadmill walking (70% peak O(2) consumption, 500 kcal expenditure). Significant findings (P < 0.05 for all) for plasma volume-adjusted lipid and enzyme variables were that TC, low-density-lipoprotein cholesterol, and cholesterol ester transfer protein activity were higher in the HC group but did not influence the lipid responses to exercise. Across groups, TC was transiently reduced immediately after exercise but returned to baseline levels by 24 h postexercise. Decreases in triglyceride and increases in high-density-lipoprotein cholesterol (HDL-C) and HDL(3)-C were observed 24 h after exercise and lasted through 48 h. Lipoprotein lipase activity was elevated by 24 h and remained elevated 48 h after exercise. HDL(2)-C, cholesterol ester transfer protein activity, hepatic triglyceride lipase, and lecithin: cholesterol acyltransferase activities did not change after exercise. These data indicate that the exercise-induced changes in HDL-C and triglyceride are similar in HC and normocholesterolemic men and may be mediated, at least in part, by an increase in lipoprotein lipase activity.     

Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man

Twenty patients consumed a liquid diet in which the predominant fatty acids were either saturated (Sat), monounsaturated (Mono), or polyunsaturated (Poly). The fats in these three diets comprised 40% of total calories and consisted of palm oil, high-oleic safflower oil, and high-linoleic safflower oil, respectively. During the third and fourth week of each dietary period, multiple samples of blood were taken and were analyzed for plasma total cholesterol (TC), triglycerides (TG), and cholesterol in lipoprotein fractions (VLDL-C, LDL-C, and HDL-C). Twelve of the patients had normal TG levels; in these patients, both Mono and Poly diets caused statistically significant and equal lowerings of plasma LDL-C, but the Poly diet lowered HDL-C levels more frequently than did the Mono diet. Neither diet changed the level of plasma TG. The proportions of total protein and the various lipid components in isolated fractions (VLDL, IDL, LDL, HDL) were not altered by the two diets. Eight patients had hypertriglyceridemia; these individuals showed considerable variability in response to Mono and Poly diets. Although there was a trend towards reductions in TC and LDL-C levels by both types of unsaturated fats, the changes were inconsistent; furthermore, HDL-C concentrations were low on the Sat diet and were unaffected by either the Mono or the Poly diet. The results of this study show that oleic acid is as effective as linoleic acid in lowering LDL-C levels in normo-triglyceridemic patients, and oleic acid seemingly reduces HDL-C levels less frequently than does linoleic acid. Neither type of unsaturated fat had striking effects on lipoprotein levels of hypertriglyceridemic patients.     

Extreme decrease of linoleic acid in renal medulla from rats after a diet supplemented with cod liver oil

Spontaneously hypertensive (SHR) and normotensive rats were fed a diet supplemented with linseed oil or cod liver oil for 22 weeks. The most remarkable finding was an extreme fall of linoleic acid in lipids from renal medulla after cod liver oil supplementation. In free fatty acids (FFA) eicosatrienoic acid (C2): 3n-9) appeared increased as a sign of essential fatty acid (EFA) deficiency.     

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.     

Serum selenium,glutathione peroxidase,lipids, and human liver microsomal enzyme activity

This study evaluated selenium status in relation to lipid peroxidation, liver microsomal function, and serum lipids in humans. Serum selenium concentration, glutathione peroxidase (GSH-Px) activity, liver microsomal enzyme activity, assessed by plasma antipyrine clearance (AP-CL) rate, and serum lipids were determined in 23 healthy subjects in a double-blind placebo-controlled trial of selenium supplementation. The low selenium concentration (74.0±14.2 μg/L, mean±SD) is attributable to the low selenium content of the diet. Subjects with the lowest selenium levels (n=11) had reduced serum GSH-Px activity, AP-CL rate, high-density lipoprotein cholesterol (HDL-C), and total cholesterol (T-C) as compared with subjects with higher selenium concentrations (n=12). Low AP-CL rates were associated with low HDL-C: T-C ratios. Selenium supplementation, 96 μg/d for 2 wk, increased serum selenium, GSH-Px activity, and the HDL-C: T-C ratio. The results suggest that a low serum selenium level is associated with a decrease in liver microsomal enzyme activity and serum HDL-C and T-C concentrations. Selenium supplementation in subjects with low serum selenium may favorably influence relations between serum lipoproteins connected with the development of atherosclerotic vascular disease.     

Beneficial effects of alpha linolenic acid rich flaxseed oil on growth performance and hepatic cholesterol metabolism in high fat diet fed rats

The purpose of the study was to investigate the effect of flaxseed oil (FO), rich in alpha-linolenic acid (ALA) (18:3 n-3) on growth parameters and lipid metabolism of rats fed with high fat diet. High fat diet (HFD) resulted in significant alterations in hepatic lipids, increase in body weight gain and negative effect on lipoprotein metabolism. FO supplementation significantly lowered the increase in body weight gain, liver weight, plasma cholesterol, triglycerides, phospholipids, free fatty acids, high-density lipoprotein (HDL), low-density lipoprotein-cholesterol (LDL-C), very low-density lipoprotein (VLDL), LDL/HDL and TC/HDL ratio in HFD fed rats. FO significantly reduced the hepatic and plasma lipid levels indicating its hypolipidemic activity. On the other hand, oral administration of FO exhibited lower plasma lipoprotein profile as compared to HFD rats. Hepatic protection by FO is further substantiated by the normal liver histological findings in HFD fed rats. These data suggest that FO participate in the normal regulation of plasma lipid concentration and cholesterol metabolism in liver. No adverse effect of FO on growth parameters and plasma lipids in rats fed with fat-free diet. The results of the present study demonstrate that FO may be developed as a useful therapy for hyperlipidemia through reducing hepatic lipids, thereby proving its hypolipidemic activity.     

Corn fiber oil lowers plasma cholesterol levels and increases cholesterol excretion greater than corn oil and similar to diets containing soy sterols and soy stanols in hamsters

The aims of this study were to compare the cholesterol-lowering properties of corn fiber oil (CFO) to corn oil (CO), whether the addition of soy stanols or soy sterols to CO at similar levels in CFO would increase CO's cholesterol-lowering properties, and the mechanism(s) of action of these dietary ingredients. Fifty male Golden Syrian hamsters were divided into 5 groups of 10 hamsters each, based on similar plasma total cholesterol (TC) levels. The first group of hamsters was fed a chow-based hypercholesterolemic diet containing either 5% coconut oil + 0.24% cholesterol (coconut oil), 5% CO, 5% CFO, 5% CO + 0.6% soy sterols (sterol), or 5% CO + 0.6% soy stanols (stanol) in place of the coconut oil for 4 weeks. The stanol diet significantly inhibited the elevation of plasma TC compared to all other dietary treatments. Also, the CFO and sterol diets significantly inhibited the elevation of plasma TC compared to the CO and coconut oil diets. The CFO, sterol, and stanol diets significantly inhibited the elevation of plasma non-high density lipoprotein cholesterol compared to the CO and coconut oil diets. The stanol diet significantly inhibited the elevation of plasma high density lipoprotein cholesterol (HDL-C) compared to all other dietary treatments. The sterol diet significantly inhibited the elevation of plasma HDL-C compared to the CO and coconut oil diets, whereas the CFO diet significantly inhibited the elevation of plasma HDL-C compared to the coconut oil diet only. No differences were observed between the CFO and CO for plasma HDL-C. There were no differences observed between groups for plasma triglycerides. The CO and CFO diets had significantly less hepatic TC compared to the coconut oil, sterol, and stanol diets. The CO and CFO diets had significantly less hepatic free cholesterol compared to the sterol and stanol diets but not compared to the coconut oil diet; whereas the coconut oil and sterol diets had significantly less hepatic free cholesterol compared to the stanol diet. The CFO, sterol, and stanol diets excreted significantly more fecal cholesterol compared to the coconut oil and CO diets. In summary, CFO reduces plasma and hepatic cholesterol concentrations and increases fecal cholesterol excretion greater than CO through some other mechanism(s) in addition to increase dietary sterols and stanols-possibly oryzanols.     

Effect of diazinon, an organophosphate insecticide, on plasma lipid constituents in experimental animals

There has been increasing interest in studying the various effects of organophosphate insecticides in humans and experimental animals. Only a few data are available on the effect of the organophosphate insecticide, diazinon, on lipid metabolism. The aim of this study was to evaluate the effect of diazinon on plasma lipid constituents in mammalian animals. The plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and phospholipids (PL) were measured in albino rats that were orally treated with a single dose of diazinon at a level of LD(50) or with repeated daily doses at the levels of 1/2, 1/8, and 1/32 LD(50) for 2, 8, and 32 days, respectively. After a 24 h post-treatment with a single LD(50) dose of diazinon, TC was not significantly changed, the HDL-C and PL levels were significantly decreased, but the LDL-C and TG levels were significantly increased. Separate daily oral administrations of diazinon at 1/2 LD(50), 1/8 LD(50), and 1/32 LD(50) doses resulted in a significant decrease in HDL-C and PL, with no significant change in TG. The LDL-C levels were significantly increased and TC showed no significant change with 1/2 LD(50) and 1/32 LD(50) doses of diazinon, whereas a significant decrease in the levels of TC, HDL-C, as well as LDL-C, was observed with the 1/8 LD(50) dose. These data suggest that diazinon may interfere with lipid metabolism in mammals.     

Experimental hyperthyroidism in man: effects on plasma lipoproteins, lipoprotein lipase and hepatic lipase

We have studied the effects of triiodothyronine administration (20-40 micrograms three times daily over one week) in six healthy young men, on the activities of lipoprotein lipase and hepatic lipase and on plasma lipoprotein concentrations. Hepatic lipase activity in post-heparin plasma rose by 46 +/- 25% (p less than 0.025), whereas the activity of lipoprotein lipase did not change significantly. Plasma cholesterol concentrations decreased by about 20% (p less than 0.025), whereas there was no change in plasma triglyceride levels. The fall in plasma cholesterol could be accounted for by a reduction of HDL cholesterol (-11%, p less than 0.025) as well as LDL cholesterol (-27%, p less than 0.025). The data emphasize the role of hepatic lipase in the lipoprotein alterations associated with thyroid dysfunction.     

Effects of garlic extract consumption on blood lipid and oxidant/antioxidant parameters in humans with high blood cholesterol

Effects of garlic extract supplementation on blood lipid profile and oxidant/antioxidant status were investigated in volunteer subjects with high blood cholesterol. A total of 23 volunteer subjects with high blood cholesterol (>5.98 mmol/L) participated in the study. Of them, 13 patients were evaluated as a hypertensive group and the others a normotensive group. Before (first sample) and after (second sample) garlic extract consumption for 4 months, routine blood analyses including lipid parameters and liver and kidney function tests were performed. Additionally, blood oxidant (malondialdehyde [MDA], oxidation resistance [OR]), and antioxidant (antioxidant potential [AOP], nonenzymatic superoxide radical scavenger activity [NSSA]) parameters were measured. Serum total cholesterol, low-density lipoprotein (LDL) and very-low-density lipoprotein (VLDL) cholesterols, and triglyceride levels were found to be significantly lowered, but HDL high-density lipoprotein cholesterol level increased after the extract use. The total:HDL cholesterol ratio was also found to be significantly decreased after the extract use. There were no meaningful differences with regard to other routine biochemical parameters. Additionally, blood AOP, OR, and NSSA values were found increased and MDA level decreased in the second samples relative to the first ones. Systolic and diastolic blood pressure values were also found to be significantly lowered after extract supplementation in the hypertensive group, but no similar changes were observed in the normotensive group. We conclude that garlic extract supplementation improves blood lipid profile, strengthens blood antioxidant potential, and causes significant reductions in systolic and diastolic blood pressures. It also leads to a decrease in the level of oxidation product (MDA) in the blood samples, which demonstrates reduced oxidation reactions in the body.     

Differential effects of dietary fat on chick plasma and liver composition and HMG-CoA reductase activity

The comparative effects of diet supplementation with 10% saturated fat rich in 12:0 and 14:0 fatty acids (coconut oil), without and with 1% added cholesterol, and with 10% unsaturated fat rich in n-3 polyunsaturated fatty acids (menhaden oil) on cholesterol metabolism in neonatal chicks were examined to clarify the different mechanisms of their hyper- and hypolipidemic action. Supplementation of coconut oil produced a significant hypercholesterolemia after 7 days of treatment, with a similar increase in the amount of both free and esterified cholesterol. Supplementation of coconut oil plus cholesterol produced a higher increase of plasma cholesterol levels (approximately two to three times higher than those found with standard diet). However, supplementation of menhaden oil induced a significant decrease in total cholesterol after only 2 weeks of treatment. Levels of plasma triglycerides did not change by coconut oil addition to the diet, but a significant increase was observed after coconut oil plus cholesterol feeding. Menhaden oil produced a transient decrease in plasma triglycerides. Hepatic 3-hydroxy-3-methylglutaryl-CoA reductase activity did not change with coconut oil treatment. However, both coconut oil plus cholesterol and menhaden oil supplemented diets drastically decreased reductase activity after 1 week of dietary manipulation. These results show that different nutrients with the same inhibitory effect on reductase activity produced opposite effects on plasma cholesterol content, suggesting the existence of important differences in the regulatory mechanisms implied in cholesterol biosynthesis and its accumulation in plasma.     

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.     

Ameliorative role of atorvastatin on methionine-induced hyperhomocysteinemia and hematological changes in albino rats

Methionine (1g/kg, po) administration to pathogenic control rats for 30 days significantly increased the levels of homocysteine, total cholesterol (TC), low density lipoprotein (LDL-C), very low density lipoprotein (VLDL-C) and triglycerides (TGs) and decreased the levels of high density lipoprotein (HDL-C) in serum. Hematological observations of the peripheral blood smears of pathogenic rats fed with methionine also showed crenation of RBCs cell membrane and significant increase in total leukocyte count, differential leukocyte count and platelet counts with significant decrease in the mean hemoglobin levels as compared to vehicle control rats. Administration of atorvastatin (0.2 mg/kg/po) to hyperhomocysteinemic rats significantly decreased the levels of homocysteine, TC, TGs, LDL-C and VLDL-C and increased the levels of HDL-C in serum. The present results provide clear evidence that oral treatment with atorvastatin exhibit homocysteine and lipid lowering activity and also reversal of hematological changes induced by methionine in albino rats.     

Atherogenic lipid profile is a feature characteristic of patients with early rheumatoid arthritis: effect of early treatment--a prospective, controlled study

We investigated lipid profiles and lipoprotein modification after immuno-intervention in patients with early rheumatoid arthritis (ERA). Fifty-eight patients with ERA who met the American College of Rheumatology (ACR) criteria were included in the study. These patients had disease durations of less than one year and had not had prior treatment for it. Smokers or patients suffering from diabetes mellitus, hypothyroidism, liver or kidney disease, Cushing's syndrome, obesity, familiar dyslipidemia and those receiving medications affecting lipid metabolism were excluded from the study. Sixty-three healthy volunteers (controls) were also included. Patients were treated with methotrexate and prednisone. Lipid profiles, disease activity for the 28 joint indices score (DAS-28) as well as ACR 50% response criteria were determined for all patients. The mean DAS-28 at disease onset was 5.8 +/- 0.9. After a year of therapy, 53 (91.3%) patients achieved the ACR 20% response criteria, while 45 (77.6%) attained the ACR 50% criteria. In addition, a significant decrease in the DAS-28, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were observed. ERA patients exhibited higher serum levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and triglycerides, whereas their serum high-density lipoprotein cholesterol (HDL-C) levels were significantly lower compared to controls. As a consequence, the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was significantly higher in ERA patients compared to controls. After treatment, a significant reduction of the atherogenic ratio of TC/HDL-C as well as that of LDL-C/HDL-C was observed, a phenomenon primarily due to the increase of serum HDL-C levels. These changes were inversely correlated with laboratory changes, especially CRP and ESR. In conclusion, ERA patients are characterized by an atherogenic lipid profile, which improves after therapy. Thus, early immuno-intervention to control disease activity may reduce the risk of the atherosclerotic process and cardiovascular events in ERA patients.     

Effect of α-Lipoic Acid on Lipid Profile in Rats Fed a High-Fructose Diet

This study investigated the effect of administration of α-lipoic acid (LA) on lipid metabolism in high fructose–fed insulin-resistant rats. High-fructose feeding (60 g/100 g diet) to normal rats resulted in a significant increase in the concentrations of cholesterol, triglycerides (TGs), free fatty acids (FFAs), and phospholipids in plasma, liver, kidney, and skeletal muscle. Reduced activities of lipoprotein lipase (LPL) and lecithin cholesterol acyl transferase (LCAT) and increased activity of the lipogenic enzyme hydroxymethylglutaryl–coenzyme A (HMG-CoA) reductase were observed in plasma and liver. High-density lipoprotein cholesterol (HDL-C) was significantly lowered and very low-density lipoprotein cholesterol (VLDL-C) and low-density lipoprotein cholesterol (LDL-C) were significantly elevated. Treatment with LA (35 mg/kg body weight intraperitoneal) reduced the effects of fructose. The rats showed near-normal levels of lipid components on plasma and tissues. Activities of key enzymes of lipid metabolism were also restored to normal values. Cholesterol distribution in the plasma lipoproteins was normalized, resulting in a favorable lipid profile. This study demonstrates that LA can alter lipid metabolism in fructose-fed insulin-resistant rats and may have implications in the treatment of insulin resistance.     

Differential roles of breakfast and supper in rats of a daily three-meal schedule upon circadian regulation and physiology

The timing of meals has been suggested to play an important role in circadian regulation and metabolic health. Three meals a day is a well-established human feeding habit, which in today's lifestyle may or may not be followed. The aim of this study was to test whether the absence of breakfast or supper significantly affects the circadian system and physiological function. The authors developed a rat model for their daily three meals study, whereby animals were divided into three groups (three meals, TM; no first meal, NF; no last meal, NL) all fed with the same amount of food every day. Rats in the NF group displayed significantly decreased levels of plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose in the activity phase, accompanied by delayed circadian phases of hepatic peripheral clock and downstream metabolic genes. Rats in the NL group showed lower concentration of plasma TC, HDL-C, and glucose in the rest phase, plus reduced adipose tissue accumulation and body weight gain. Real-time polymerase chain reaction (PCR) analysis indicated an attenuated rhythm in the food-entraining pathway, including down-regulated expression of the clock genes Per2, Bmal1, and Rev-erbα, which may further contribute to the delayed and decreased expression of FAS in lipogenesis in this group. Our findings are consistent with the conclusion that the daily first meal determines the circadian phasing of peripheral clocks, such as in the liver, whereas the daily last meal tightly couples to lipid metabolism and adipose tissue accumulation, which suggests differential physiological effects and function of the respective meal timings.     

Biological and environmental sources of variation in plasma lipids and lipoproteins: the Jerusalem Lipid Research Clinic

We have previously described a general pattern of homogeneity in genetic and cultural determinants of blood lipids and lipoproteins among the major origin groups in the Israeli population. This paper reports on these determinants of total plasma cholesterol (TC), triglyceride (TG), low- and high-density lipoprotein cholesterol (LDL-C, HDL-C), and of the HDL-C/TC ratio, estimated from the total sample of 4,000 families whose members were examined in the Jerusalem Lipid Research Clinic. Both genetic (h2) and cultural (c2) components of inheritance were significant for all lipid variables. Under the most parsimonious model genetic heritability (h2) ranges from 0.45 for LDL-C, 0.47 for HDL-C to 0.64 for HDL-C/TC ratio. Cultural heritability (c2) was 0.03 for LDL-C, 0.04 for TC, 0.05 for TG and 0.07 for HDL-C and HDL-C/TC ratio. Within this population, as in others, genetic factors appear to be the major determinants of lipid variation, suggesting relative homogeneity of environmental correlates of plasma lipids.     

Hepatic proprotein convertases modulate HDL metabolism

The risk of atherosclerosis is inversely associated with plasma levels of high-density lipoprotein cholesterol (HDL-C). However, HDL metabolism is incompletely understood, and there are few effective approaches to modulate HDL-C levels. Here we show that inhibition in the liver of the classical proprotein convertases (PCs), but not the atypical PCs S1P and PCSK9, decreases plasma HDL-C levels. This metabolic effect of hepatic PCs is critically dependent on expression of endothelial lipase (EL), an enzyme that directly hydrolyzes HDL phospholipids and promotes its catabolism. Hepatic PCs reduce EL function through direct inactivating cleavage of EL as well as through activating cleavage of angiopoietin-like protein 3 (ANGPTL3), an endogenous inhibitor of EL. Thus, inhibition of hepatic PCs results in increased EL activity, leading to reduced HDL-C as well as impaired reverse cholesterol transport. The hepatic PC-ANGPTL3-EL-HDL pathway is therefore a novel mechanism controlling HDL metabolism and cholesterol homeostasis.