Zinc deficiency and the activities of lipoprotein lipase in plasma and tissues of rats force-fed diets with coconut oil or fish oil

The present study was performed to investigate the effect of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and tissues of rats fed diets containing either coconut oil or fish oil as dietary fat, using a bifactorial experimental design. To ensure an adequate food intake, all the rats were force-fed by gastric tube. Experimental diets contained either 0.8 mg zinc/kg (zinc-deficient diets) or 40 mg zinc/kg (zinc-adequate diets). The effects of zinc deficiency on the activities of lipoprotein lipase in postheparin serum and postprandial triglyceride concentrations and distribution of apolipoproteins in serum lipoproteins depended on the type of dietary fat. Zinc-deficient rats fed the coconut oil diet exhibited a reduced activity of lipoprotein lipase in postheparin serum and adipose tissue, markedly increased concentrations of triglycerides in serum, and a markedly reduced content of apolipoprotein C in triglyceride-rich lipoproteins and high density lipoproteins compared with zinc-adequate rats fed coconut oil. By contrast, zinc-deficient rats fed the fish oil diet did not exhibit reduced activities of lipoprotein lipase in postheparin serum and adipose tissue and increased concentrations of serum lipids compared with zinc-adequate rats fed the fish oil diet. This study suggests that a reduced activity of lipoprotein lipase might contribute to increased postprandial concentrations of serum triglycerides observed in zinc-deficient animals. However, it also demonstrates that the effects of zinc deficiency on lipoprotein metabolism are influenced by dietary fatty acids.     

The effects of fasting and refeeding on serum parathormone and calcitonin concentrations in young and old male rats.

Although fasting and refeeding reveal the existence of age-related changes in carbohydrate and lipid metabolism, the effects of aging on mineral metabolism in refed animals are unknown. We therefore investigated hormonal regulation of calcium metabolism in young (4 months) and old (26 months) male rats fasted for 48 hours and then refed for 4 or 24 hours. Serum concentrations of total and ionized calcium and parathormone were similar in control young and old rats. Serum calcitonin level was higher, and the concentrations of albumin and inorganic phosphate and alkaline phosphatase activity were lower in fed old rats. In young fasted rats, the serum ionized and total calcium was decreased, and phosphate concentration was increased. In old rats, fasting resulted in the increase of serum parathormone level. Fasting reduced serum alkaline phosphatase activity to a similar extent in both age groups. In young rats, refeeding for 24h normalized serum calcium and phosphate levels and alkaline phosphatase activity, and decreased serum concentrations of PTH and calcitonin. In old refed rats, serum calcitonin concentration was raised by 77% compared to fed or fasted animals, whereas parathormone levels were normalized. Our results indicate that old fasted or refed rats maintain normal serum calcium concentration in a different way than young animals, possibly through the increase in serum levels of parathormone and/or calcitonin. Thus, dietary manipulations such as fasting and refeeding constitute an interesting model for the investigation of the effects of aging on the hormonal regulation of serum calcium level.     

Glycosylphosphatidylinositol-specific phospholipase D influences triglyceride-rich lipoprotein metabolism

Glycosylphosphatidylinositol-specific phospholipase D (GPI-PLD) is a minor HDL-associated protein. Because many minor HDL-associated proteins exchange between different lipoprotein classes during the postprandial state and are also involved in triglyceride (TG) metabolism, we hypothesized that GPI-PLD may play a role in the metabolism of TG-rich lipoproteins. To test this hypothesis, we examined the distribution of GPI-PLD among lipoprotein classes during a fat tolerance test in C57BL/6 and LDL receptor-deficient (LDLR(-/-)) mice fed either a chow or high-fructose diet. In the fasting state in wild-type mice fed a chow diet, GPI-PLD was only present in HDL, whereas in LDLR(-/-) mice GPI-PLD was present in HDL and intermediate-density lipoproteins (IDL)/LDL. During the fat tolerance test, there was no change in total serum GPI-PLD levels in either model; however, a significant amount of GPI-PLD appeared in both VLDL (0.5-1% of total GPI-PLD) and IDL/LDL (5-10% of total GPI-PLD) in both models. The high-fructose diet increased both fasting and postprandial TG and serum GPI-PLD levels in both strains as well as the amount of GPI-PLD in VLDL. To determine whether GPI-PLD plays a direct role in TG metabolism, we increased liver GPI-PLD expression in C57BL/6 mice by adenovirus-mediated gene transfer, which resulted in a sevenfold increase in serum GPI-PLD levels. This change was associated with an increase in fasting (30%) and postprandial TG (50%) and a twofold reduction in TG-rich lipoprotein catabolism compared with saline or control adenovirus-treated mice. These studies demonstrate that GPI-PLD affects serum TG levels by altering catabolism of TG-rich lipoproteins.     

Orthostatic and postprandial hypotension in patients aged 70 years or older admitted to a medical ward

The aim of this study was to determine the prevalence of orthostatic (OH) and postprandial hypotension (PPH) in Dutch elderly patients admitted to a medical ward and to explore patient characteristics associated with OH and PPH: symptoms, medications and comorbidity. We studied 50 patients, mean age 78.8 years, 68% female. Orthostatic hypotension (OH) was defined as a decrease of systolic blood pressure (BP) > or = 20 or diastolic > or = 10 mm Hg after 3 minutes of standing. To diagnose postprandial hypotension (PPH) BP was measured sitting before and 30 minutes after the start of patient's noon meal, the same criteria were applied. We registered changes in BP, pulse rate, complaints, reason for hospitalization, medication and comorbidity: hypertension, diabetes mellitus and Parkinson(ism). We found OH in 24% of the patients, PPH was diagnosed more frequently: in 34%. 10% had both, but there were no relations between OH and PPH. In none of the patients OH and PPH were measured before our assessment. Pulse rate increased respectively 8 and 3/min. With OH and PPH. Both subjective and objective complaints were significantly associated with OH, where as only subjective non-specific complaints were associated with PPH. Objective complaints were very rare in PPH. OH and PPH were not significantly associated with medication use and comorbidity. PPH and OH are common in hospitalized elderly patients. OH is more often symptomatic than PPH. We found no relationship with medication use or comorbidity. According to research literature, however, OH and PPH are associated with higher morbidity, mortality and possibly cognitive decline. Therapeutic measures must be considered, especially in the presence of comorbidity such as significant carotid artery occlusion.     

Model-Based Quantification of the Systemic Interplay between Glucose and Fatty Acids in the Postprandial State

In metabolic diseases such as Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, the systemic regulation of postprandial metabolite concentrations is disturbed. To understand this dysregulation, a quantitative and temporal understanding of systemic postprandial metabolite handling is needed. Of particular interest is the intertwined regulation of glucose and non-esterified fatty acids (NEFA), due to the association between disturbed NEFA metabolism and insulin resistance. However, postprandial glucose metabolism is characterized by a dynamic interplay of simultaneously responding regulatory mechanisms, which have proven difficult to measure directly. Therefore, we propose a mathematical modelling approach to untangle the systemic interplay between glucose and NEFA in the postprandial period. The developed model integrates data of both the perturbation of glucose metabolism by NEFA as measured under clamp conditions, and postprandial time-series of glucose, insulin, and NEFA. The model can describe independent data not used for fitting, and perturbations of NEFA metabolism result in an increased insulin, but not glucose, response, demonstrating that glucose homeostasis is maintained. Finally, the model is used to show that NEFA may mediate up to 30–45% of the postprandial increase in insulin-dependent glucose uptake at two hours after a glucose meal. In conclusion, the presented model can quantify the systemic interactions of glucose and NEFA in the postprandial state, and may therefore provide a new method to evaluate the disturbance of this interplay in metabolic disease.     

Effects of an alpha-glucosidase inhibitor, acarbose, on blood glucose and serum lipids in streptozotocin-induced diabetic rats

Effects of either a single dose or a long-term administration of an alpha-glucosidase inhibitor, acarbose, on blood glucose, cholesterol concentrations in serum lipoprotein fractions, triglycerides and free fatty acids were examined in streptozotocin-induced diabetic rats. In experiment 1, starch loading tests were performed with or without adding acarbose. The addition of acarbose (0.75 mg per kg of body weight or over) significantly reduced the elevation of blood glucose levels. In experiment 2, the animals were divided into three groups: Group A fed on a control diet, Group B fed on a diet containing 5 mg acarbose in 100 g of diet and Group C fed on a diet containing 20 mg acarbose in 100 g of diet. The food intake in Group C was significantly reduced by 22% as compared to Group A, while the food intake in Group B showed no change. The high dose of acarbose showed a tendency to lower fasting blood glucose levels, but the difference was statistically insignificant. However, postprandial glucose levels in Group C at each period examined and in Group B at 30 days were significantly lower than the counterparts in Group A. Acarbose caused a dose-dependent decrease in serum total cholesterol levels and HDL-cholesterol: total cholesterol ratios were elevated in Group B and C. Serum triglyceride levels in Group B and C were extremely lower than those in Group A on and after 20 days. These results indicate that the addition of acarbose to the diet induces a decrease in postprandial blood glucose levels and simultaneously causes an improvement in lipid metabolism of streptozotocin-induced diabetic rats.     

Acute intake of a high-fructose diet alters the balance of adipokine concentrations and induces neutrophil influx in the liver

The postprandial state is a period of metabolic fluxes, biosynthesis and oxidative metabolism. A considerable amount is known about the inflammatory response to the chronic consumption of fructose, but little is known about its effects in the postprandial state. The aim of the present study was to investigate the inflammatory effects of a single meal containing fructose on healthy mice. Male BALB/c and LysM-eGFP mice at 12–14 weeks were divided into three groups: fasted, control (mice fed with a sucrose-containing diet) and fructose (mice fed with a fructose-containing diet). One, 2 or 4 h postprandial, the BALB/c mice were killed, and samples were collected. LysM-eGFP mice were submitted to intravital microscopy. The fed mice showed a low-grade inflammatory response apart from dietary composition, which was characterized by increased numbers of leukocytes and high serum concentrations of pentraxin 3, leptin and resistin. TNF-α and CCL2 concentrations rose in the liver after the meal. IL-6 concentration increased and IL-10 decreased in the adipose tissue of the fed mice. Mice fed with the fructose-containing diet showed an intensification of the inflammatory response. Furthermore, the adiponectin concentration dropped, and the liver influx of neutrophils increased after fructose intake. Overall, this study showed a rapid increase in the systemic and tissue-specific immune response after a balanced meal. The study also showed an increased neutrophil influx in liver associated with an imbalance of adipokine concentrations and an increase of cytokine in the liver and adipose tissue following a fructose-containing meal.     

Increased postprandial homocysteinemia in a group of depressed patients

Summary Elevated tissue and serum concentrations of homocysteine (HCY) are associated with neuropsychiatric disorders as well as with premature occlusive vascular disease, as seen in homocystinuria. In order to study dietary-related modifications in plasma HCY, total HCY was assayed in the fasted state and 2 hr after meals in 12 depressed female patients aged 54 to 81 yr and in 12 female controls aged 50 to 85 yr. Fasting HCY was also studied in 4 patients with dementia. Postprandial HCY varied only slightly in the controls compared with their fasting values, whereas a significant increase was noted in the depressives. To study the influence of normal and low protein diets on this abnormality, fasting and postprandial HCY were investigated in 4 of the depressives after one week of a normal diet, after a week on a diet without meat, fish or eggs, and then again after return to a normal diet for one week. Persistence of the abnormal increase in postprandial HCY in 2 of these 4 patients while on the low-protein diet may have been due to an inherited defect in HCY metabolism. Folate deficiency can also cause hyperhomocysteinemia, and as folate supplements constantly lower HCY concentrations, nutritional counseling and folate therapy might prove helpful in the treatment of depression.     

Effects of glucose ingestion on postprandial lipemia and triglyceride clearance in humans

To determine whether the metabolism of diet-derived triglycerides (TG) is acutely regulated by the consumption of insulinogenic carbohydrates, we measured the effects of glucose ingestion on oral and intravenous fat tolerance, and on serum triglyceride concentrations obtained during duodenal fat perfusion. Postprandial lipemia was diminished by the ingestion of 50 g (148 +/- 121 mg.dl-1 x 7 h-1 vs 192 +/- 124 mg.dl-1 x 7 h-1, P less than 0.05) and 100 g (104 +/- 106 mg.dl-1 x 7 h-1 vs 171 +/- 104 mg.dl-1 x 7 h-1, P less than 0.05) glucose. Peak postprandial TG concentrations occurred later after meals containing glucose and fat than after meals containing fat alone. This effect could be reproduced when an iso-osmotic quantity of urea was substituted for glucose in the test meal. Starch ingestion had no discernible effect on postprandial lipemia. Intravenous fat tolerance was similar before (4.9 +/- 1.2%.min-1) and 2 h (4.4 +/- 1.3%.min-1) and 4 h (4.8 +/- 1.5%.min-1) after 50 g glucose ingestion. During duodenal fat perfusion, glucose ingestion caused a progressive decrease in plasma triglyceride concentrations. These data suggest that glucose ingestion diminishes postprandial lipemia in a dose-dependent manner, but that this effect is not due to increased clearance of triglyceride from the circulation. The hypotriglyceridemic effects of glucose appear to reflect delayed gastric emptying and decreased hepatic secretion of triglyceride.     

Protein phosphatase 2A in Saccharomyces cerevisiae: effects on cell growth and bud morphogenesis.

We have cloned three genes for protein phosphatases in the yeast Saccharomyces cerevisiae. Two of the genes, PPH21 and PPH22, encode highly similar proteins that are homologs of the mammalian protein phosphatase 2A (PP2A), while the third gene, PPH3, encodes a new PP2A-related protein. Disruptions of either PPH21 or PPH22 had no effects, but spores disrupted for both genes produced very small colonies with few surviving cells. We conclude that PP2A performs an important function in yeast cells. A disruption of the third gene, PPH3, did not in itself affect growth, but it completely prevented growth of spores disrupted for both PPH21 and PPH22. Thus, PPH3 provides some PP2A-complementing activity which allows for a limited growth of PP2A-deficient cells. Strains were constructed in which we could study the phenotypes caused by either excess PP2A or total PP2A depletion. We found that the level of PP2A activity has dramatic effects on cell shape. PP2A-depleted cells develop an abnormal pear-shaped morphology which is particularly pronounced in the growing bud. In contrast, overexpression of PP2A produces more elongated cells, and high-level overexpression causes a balloonlike phenotype with huge swollen cells filled by large vacuoles.     

Effect of chromium nicotinic acid supplementation on selected cardiovascular disease risk factors

The effects of daily supplemental chromium (200 μg) complexed with 1.8 mg nicotinic acid on plasma glucose and lipids, including total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, were assessed in 14 healthy adults and 5 adults with noninsulin-dependent diabetes mellitus (NIDDM) using a double-blind crossover study with 8-wk experimental periods. Eight of the 14 healthy subjects and all 5 subjects with NIDDM also underwent an oral glucose tolerance test with assessment of 90 min postprandial plasma glucose and insulin concentrations. No statistically significant effects of chromium nicotinic acid supplementation were found on plasma insulin, glucose, or lipid concentrations, although chromium nicotinic acid supplementation slightly lowered fasting plasma total and LDL cholesterol, triglycerides, and glucose concentrations, and 90-min postprandial glucose concentrations in individuals with NIDDM.     

Fenofibrate, a peroxisome proliferator-activated receptor α agonist, alters triglyceride metabolism in enterocytes of mice

Fenofibrate, a drug in the fibrate class of amphiphathic carboxylic acids, has multiple blood lipid modifying actions, which are beneficial to the prevention of atherosclerosis. One of its benefits is in lowering fasting and postprandial blood triglyceride (TG) concentrations. The goal of this study was to determine whether the hypotriglyceridemic actions of fenofibrate in the postprandial state include alterations in TG and fatty acid metabolism in the small intestine. We found that the hypotriglyceridemic actions of fenofibrate in the postprandial state of high-fat (HF) fed mice include a decrease in supply of TG for secretion by the small intestine. A decreased supply of TG for secretion was due in part to the decreased dietary fat absorption and increased intestinal fatty acid oxidation in fenofibrate compared to vehicle treated HF fed mice. These results suggest that the effects of fenofibrate on the small intestine play a critical role in the hypotriglyceridemic effects of fenofibrate.     

Chronic dietary fat and cholesterol inhibit the normal postprandial stimulation of plasma cholesterol metabolism

The response of parameters of plasma cholesterol metabolism was studied in baboons adapted either to a low-fat, low-cholesterol diet or a high-fat, high-cholesterol diet. Animals adapted to the low-fat diet responded to a single low-fat or high-fat meal, as do normal humans, by a stimulation of cholesterol transport from blood cells to plasma, a stimulation of esterification of cholesterol, and a stimulation of cholesteryl ester transfer to very low and low density lipoproteins. While fasting rates of esterification and transfer increased as a result of diet-induced hypercholesterolemia, the postprandial response was reversed, so that postprandial metabolism was characterized by a movement of cholesterol from plasma to blood cells, an inhibition of cholesterol esterification, and a net transfer of cholesteryl esters from VLDL and LDL to HDL. These data indicate that the effects of postprandial lipemia on plasma cholesterol metabolism critically depend upon fasting plasma cholesterol levels.     

How does endogenous and exogenous cholesterol influence the lipoprotein metabolism. Effects of long-term endurance exercise, and accumulation of cholesterol ester on the aortic wall

We first supplied the rats with sucrose which accelerates the synthesis of the very low density lipoprotein (VLDL). After 5 weeks ingestion, we investigated the effects of the long-term endurance exercise on the concentration of the endogenous cholesterol and on the accumulation of the cholesterol ester on the arterial wall, with the emphasis on lipid metabolism, especially on lipoprotein metabolism. The concentrations of triglyceride and VLDL in sucrose-ingested group were significantly higher than control. As to the aortic wall, the total amount of cholesterol ester was increased (almost twice). Regular endurance exercise over long period after serum and hepatic lipids had already reached a high level did not reduced the triglyceride in the liver but in serum. It showed be emphasized that the exercise reduces triglyceride and VLDL-cholesterol, and to this extent does contribute to alleviation of hyperlipidemia and to prevention or moderation of arteriosclerosis.     

Activation of peroxisome proliferator-activated receptor-α (PPARα) suppresses postprandial lipidemia through fatty acid oxidation in enterocytes

Activation of peroxisome proliferator-activated receptor (PPAR)-α which regulates lipid metabolism in peripheral tissues such as the liver and skeletal muscle, decreases circulating lipid levels, thus improving hyperlipidemia under fasting conditions. Recently, postprandial serum lipid levels have been found to correlate more closely to cardiovascular diseases than fasting levels, although fasting hyperlipidemia is considered an important risk of cardiovascular diseases. However, the effect of PPARα activation on postprandial lipidemia has not been clarified. In this study, we examined the effects of PPARα activation in enterocytes on lipid secretion and postprandial lipidemia. In Caco-2 enterocytes, bezafibrate, a potent PPARα agonist, increased mRNA expression levels of fatty acid oxidation-related genes, such as acyl-CoA oxidase, carnitine palmitoyl transferase, and acyl-CoA synthase, and oxygen consumption rate (OCR) and suppressed secretion levels of both triglycerides and apolipoprotein B into the basolateral side. In vivo experiments revealed that feeding high-fat-diet containing bezafibrate increased mRNA expression levels of fatty acid oxidation-related genes and production of CO₂ and acid soluble metabolites in enterocytes. Moreover, bezafibrate treatment suppressed postprandial lipidemia after oral administration of olive oil to the mice. These findings indicate that PPARα activation suppresses postprandial lipidemia through enhancement of fatty acid oxidation in enterocytes, suggesting that intestinal lipid metabolism regulated by PPARα activity is a novel target of PPARα agonist for decreasing circulating levels of lipids under postprandial conditions.     

Effects of acute administration of doxazosin on fasting and postprandial haemodynamics and lipid metabolism in healthy subjects.

The selective alpha1 -adrenoceptor antagonist doxazosin has apparently beneficial effects on insulin sensitivity and on plasma lipid concentrations. In order to understand these effects better, we investigated the acute effects of doxazosin on adipose tissue and forearm blood flow and on postprandial lipid metabolism in healthy subjects. Nine subjects were studied in a balanced, placebo-controlled design. Pulse rate, blood pressure, forearm and subcutaneous adipose tissue blood flow were measured before and for 6 h after a mixed meal, with concomitant measurements of blood metabolites and insulin. Doxazosin increased pulse rate (p = 0.02) and forearm blood flow (p < 0.01 in fasting state), and decreased vascular resistance in forearm (p < 0.05 for fasting values) and subcutaneous abdominal adipose tissue (p = 0.04). Fasting plasma non-esterified fatty acid concentrations were increased by 40 % (p < 0.05). No other metabolic effects were detected. The effects on adipose tissue vascular resistance and lipolysis (reflected in elevated non-esterified fatty acid concentrations) were unexpected, as these are usually considered to be mediated by the balance of alpha2 - and beta-adrenoceptor activity in humans. We conclude that alpha1 -adrenoceptor activity may be more important in regulation of human lipid metabolism than previously recognized.     

Effects of atorvastatin on fasting and postprandial complement component 3 response in familial combined hyperlipidemia

VLDL overproduction by enhanced hepatic FFA flux is a major characteristic of familial combined hyperlipidemia (FCHL). The postprandial complement component 3 (C3) response has been associated with impaired postprandial FFA metabolism in FCHL. We investigated the effects of 16 weeks of treatment with atorvastatin on postprandial C3 and lipid changes in 12 FCHL patients. Atorvastatin significantly lowered fasting plasma C3 and triglyceride (TG) in FCHL. Fasting TG and insulin sensitivity were the best predictors of fasting and postprandial C3. Postprandial triglyceridemia and C3 response, estimated as area under the curve (AUC), were significantly lowered by atorvastatin by 19% and 12%, respectively, albeit still elevated, compared with 10 matched controls. Postprandial FFA-AUC and postheparin plasma lipolytic activities remained unchanged after atorvastatin, suggesting no major effect on lipolysis. After atorvastatin, postprandial hydroxybutyric acid-AUC, which was elevated in untreated FCHL patients, was decreased, reaching values similar to those in controls. The present data show reduction of postprandial hepatic FFA flux in FCHL by atorvastatin, providing an additional mechanistic explanation for the reduction of VLDL secretion reported previously for atorvastatin. This was accompanied by a decrease in fasting plasma C3 concentrations and a blunted postprandial C3 response to an acute oral fat load.     

Postprandial increases in serum antioxidant capacity in older women.

Eight women were recruited for studying the effects of a meal on overall antioxidant status. Subjects resided in a metabolic research unit for two 36-h periods. During period A, subjects fasted overnight (12 h) and were then given a breakfast, a lunch, a snack, and a dinner. During period B, subjects fasted for 23 h and were then given a dinner. These meals were designed to contain negligible antioxidants. Blood samples were collected for analyzing total antioxidant capacity (TAC) and individual antioxidants. The results showed that serum TAC significantly increased by up to 23% after the consumption of the lunch and dinner during period A. Serum TAC did not increase until after the consumption of the dinner during period B. Among the antioxidants (vitamin C, alpha-tocopherol, bilirubin, and uric acid) examined, serum uric acid was the only one that showed a significant postprandial increase, which was also parallel to the postprandial response in serum TAC. These results indicate that food intake, even if low in antioxidants, can increase the serum total antioxidant activity.     

Metabolomic analysis of amino acid and energy metabolism in rats supplemented with chlorogenic acid

This study was conducted to investigate effects of chlorogenic acid (CGA) supplementation on serum and hepatic metabolomes in rats. Rats received daily intragastric administration of either CGA (60 mg/kg body weight) or distilled water (control) for 4 weeks. Growth performance, serum biochemical profiles, and hepatic morphology were measured. Additionally, serum and liver tissue extracts were analyzed for metabolomes by high-resolution ¹H nuclear magnetic resonance-based metabolomics and multivariate statistics. CGA did not affect rat growth performance, serum biochemical profiles, or hepatic morphology. However, supplementation with CGA decreased serum concentrations of lactate, pyruvate, succinate, citrate, β-hydroxybutyrate and acetoacetate, while increasing serum concentrations of glycine and hepatic concentrations of glutathione. These results suggest that CGA supplementation results in perturbation of energy and amino acid metabolism in rats. We suggest that glycine and glutathione in serum may be useful biomarkers for biological properties of CGA on nitrogen metabolism in vivo.     

The effect of IL6-174C/G polymorphism on postprandial triglyceride metabolism in the GOLDN studyboxs

Chronically elevated interleukin-6 (IL-6) affects lipid and lipoprotein metabolism. Individuals genetically predisposed to higher IL-6 secretion may be at risk of dyslipidemia, especially during the postprandial phase. We investigated the effect of genetic variants at the IL6 locus on postprandial lipemia in US Whites participating in the Genetics of Lipid Lowering Drugs and Diet Network study. Subjects were given a single fat load composed of 3% of calories as protein, 14% as carbohydrate, and 83% as fat. Blood was drawn at 0 h, 3.5 h, and 6 h to determine plasma triglyceride (TG), TG-rich lipoprotein (TRL) and lipoprotein particle size. Homozygotes (GG) and heterozygotes (CG) of the -174C/G variant displayed higher plasma IL-6 concentrations compared with major allele homozygotes (CC) (P = 0.029). GG and CG subjects showed higher fasting plasma TG (P = 0.025), VLDL (P = 0.04), and large VLDL (P = 0.02) concentrations than did CC subjects. Moreover, GG and CG subjects experienced greater postprandial response of TG (P = 0.006) and TRL, including chylomicrons (P = 0.005), total VLDL (P = 0.029), and large VLDL (P = 0.017) than did CC subjects. These results suggest that the functional polymorphism -174C>G at the IL6 locus determines the difference in both fasting and postprandial TG metabolism. This phenomenon could be responsible for the observed association of this genetic variant with cardiovascular disease risk.