Effect of medium- and long-chain triglyceride infusion on lipoprotein and hepatic lipase in healthy subjects

Plasma lipolytic activity and hydrolysis of intravenous fat were studied in six healthy subjects during infusion of a long-chain triglyceride (LCT) fat emulsion (Intralipid 20%) or of a medium-chain triglyceride (MCT)/LCT emulsion (Lipofundin MCT 20%). The fat emulsions were infused continuously at a rate of 0.17 g triglyceride kg-1 body weight (BW)h-1 for 6 h in random order at 7-day intervals. A continuous infusion of glucose (0.18 g kg-1 BW h-1) was administered for a period of 7 h and was started 1 h before the lipid infusion. Infusions of both types of fat increased plasma triglyceride (TG), free fatty acid (FFA) and lipoprotein lipase (LPL) levels and steady-state values were present during the 3rd to 5th h of infusion. MCT/LCT infusion resulted in higher plasma levels at steady-state of TG (3.63 +/- 0.45 [SEM] vs 2.73 +/- 0.45 mmol l-1; P less than 0.05), FFA (1.05 +/- 0.08 vs 0.54 +/- 0.04 mmol l-1; P less than 0.01) and LPL (4.6 +/- 0.6 vs 2.6 +/- 0.5 mU ml-1; P less than 0.05) in comparison with LCT administration. There was a positive correlation between plasma LPL activity and TG concentration (r = 0.77; P less than 0.001) when data for the two infusions were combined. Although the same amount of fat was infused on a weight basis, the molar infusion rate was 40% higher with MCT/LCT than with LCT infusion, due to differences in molecular weights (634 vs 885 Da).(ABSTRACT TRUNCATED AT 250 WORDS)     

Fat emulsions containing medium chain triglycerides in patients with sepsis syndrome: Effects on pulmonary hemodynamics and gas exchange

Fat emulsions containing medium chain triglycerides (MCT) have recently been introduced into clinical practice as a component of total parenteral nutrition. Since several authors reported increased pulmonary artery pressure and impaired gas exchange during intravenous (i.v.) fat use, in particular in septic patients, we studied the pulmonary hemodynamic and gas exchange effects of i.v. fat containg MCT and long chain triglycerides (LCT) in patients with sepsis syndrome. As the effects of fat emulsions have been attributed to increased formation of prostanoids, the production of thromboxane A₂ and prostacyclin was investigated by the determination of urinary thromboxane B₂ and 6-keto-prostaglandin F₂, respectively. The i.v. fat use did not induce any alterations in pulmonary hemodynamics and gas exchange, the distribution of ventilation and perfusion nor urinary probably content. We conclude that fat emulsions containing MCT induce little alterations in pulmonary hemodynamics and gas exchange. This result is probably due to reduced prostaglandin formation because fat emulsions containing MCT provide less prostaglandin precursors than pure LCT emulsions.     

Sex differences in serum lipids and lipoproteins at birth

In a study of 1426 males and 1391 females at birth the mean concentrations of cholesterol in total serum, in the sum of very low density and low density lipoproteins and in high density lipoprotein were significantly higher in females than in males. No sex difference was present in the concentration of triglycerides either in total serum or in the lipoprotein fractions.     

Analysis of the regenerative capacity of human serum exosomes after a simple multistep separation from lipoproteins

Due to the abundance of lipoproteins in blood, it is challenging to characterize the biological functions and components of blood‐derived extracellular vesicles. The aim of this study was to develop a multiple‐step purification protocol to separate serum exosomes from serum proteins and lipoproteins and assess their regenerative potential. Exosomes were isolated by concentrating them in human serum using ultracentrifugation (UC), followed sequentially by density gradient (DG) UC and size exclusion chromatography (SEC). Purity and characterization were assessed by western blots, Lipoprint®, enzyme‐linked immunosorbent assay, electron microscopy, mass spectrometry, and nanoparticle tracking analysis. Functionality was assessed by cell proliferation analysis and with an in vivo subcutaneous angiogenesis model. SEC alone isolated nano‐sized vesicles possessing vesicle markers TSG101 and CD9, but there was a substantial presence of apolipoprotein B, predominantly derived from very‐low‐ and intermediate‐density lipoprotein particles. This was reduced to an undetectable level using the combined UC DG SEC approach. Mass spectrometry identified 224 proteins in UC DG SEC isolates relative to the 135 from SEC, with considerable increases in exosome‐related proteins and reductions in lipoproteins. A consistent but limited increase in human dermal fibroblast proliferation and evidence of neovascularization enhancement were observed after exposure to UC DG SEC exosomes. An UC DG SEC purification protocol considerably improved the removal of lipoproteins during isolation of serum exosomes. The purified exosomes stimulated cell proliferation and potentially increased an in vivo angiogenic response. This multistep purification allows for more accurate identification of serum exosome functional activity and composition.     

Measures of fat distribution as determinants of serum lipids in healthy volunteers consuming a uniform standardized diet

The relation was investigated between body fat topology and serum lipoproteins in healthy, nonobese men and women. Twenty-four men and 24 women consumed a standardized affluent diet for 17 days. Serum was obtained after 14 and 17 days. Regression coefficients of lipids and lipoproteins with age, body mass index, measures of fat distribution, and estimates of fat areas at a cross-section of the body at the level of the umbilicus, were calculated. Waist-to-thigh circumference ratio proved to be the strongest correlate of serum lipids compared with other measures of fat distribution. Upon multiple regression analysis, the waist-to-thigh ratio proved to be a stronger predictor of total cholesterol, LDL-cholesterol and triglyceride levels in men than either age or body mass index. In women this was only true for HDL3-cholesterol. In addition, no significant relations were observed any more of age and body mass index with these serum lipids, with the exception of age for IDL-cholesterol in men. Estimates of intra-abdominal fat area showed in general a stronger correlation with serum lipids than estimates of subcutaneous fat area. It is concluded that, in non-obese subjects, fat distribution is a stronger determinant of serum lipids than either body mass index or age.     

Relation between triglycerides in human skeletal muscle and serum and the fractional elimination rate of exogenous plasma triglycerides

Muscle triglycerides, serum lipid and lipoprotein concentrations and an intravenous fat tolerance test were determined on thirteen survivors of myocardial infarction and on fourteen subjects referred to a Lipid Clinic but without myocardial infarction. The mean concentration of triglycerides in muscle and the fractional removal rate k2 of intravenous injected Intralipid were similar in patients with and without MI. In seventeen of these subjects type IV hyperlipoproteinaemia was found. In type IV patients the muscle triglyceride concentration was twice that found in patients without hypertriglyceridaemia. A negative correlation between muscle triglyceride concentration and the k2 value was found for all subjects with a correlation coefficient of -0.62 (P less than 0.001). No independent correlations were found between muscle triglyceride and serum triglyceride concentration or the triglyceride concentrations of the major lipoproteins.     

Di-, mono- and nonphytanyl triglycerides in the serum: a sensitive parameter of the phytanic acid accumulation in Refsum's disease.

The relative proportions of the diphytanyl, monophytanyl and nonphytanyl triglycerides ("triglyceride pattern"), the phytanic acid content of the triglycerides and the phytanic acid levels in the serum of 3 patients with Refsum's disease (heredopathia atactica polyneuritiformis, phytanic acid storage disease) were estimated by thin-layer chromatography, densitometry and gas chromatography, respectively. The individual triglyceride patterns were clearly dependent on the phytanic acid content of the triglycerides: the more phytanic acid in the triglycerides, the higher the percentage of the diphytanyl and the lower the percentage of the nonphytanyl triglycerides. The monophytanyl triglycerides were also related to the phytanic acid content of the triglycerides, although in a complex manner. The triglyceride pattern can be taken as a parameter of the phytanic acid accumulation in Refsum's disease to be at least as sensitive as the serum phytanic acid level in the biochemical evaluation of the efficiency of the dietary treatment.     

Comparison of the effects of two different doses of alcohol on serum lipoproteins, HDL-subfractions and apolipoproteins A-I and A-II: a controlled study

Abstract Our earlier studies have shown that heavy alcohol intake increases the serum concentration of HDL₂. The present study aimed to test which HDL subfraction is affected by moderate alcohol intake, and to examine the time- and dose-dependency of alcohol-induced changes in serum lipoproteins. Therefore, 30 or 60 g day^-1 of alcohol were given to 10 healthy male volunteers during two 3-week periods separated by an abstinence period of 3 weeks. Lipoproteins were fractioned by sequential flotation. On both doses the total HDL₃ concentrations rose progressively, the maximum increases being 10 and 25% at the end of respective drinking periods. In contrast, the HDL₂ increased slightly only on the dose of 60 g day^-1. The serum concentrations of apoprotein A-I and A-II increased on both doses but significantly only on the dose of 60 g day^-1; the increments being 22 and 35%, respectively. On the basis of these and our earlier findings we conclude that (i) the effects of heavy and moderate alcohol intake on serum HDL-subfractions are different: the former preferentially increases the HDL₂ whereas the latter augments the HDL₃; (ii) alcohol-induced changes in serum lipoproteins are both time- and dose-dependent.     

Changes in rat serum lipoproteins following ligation of the bile duct.

Lipoproteins in the serum of normal and of cholestatic rats have been studied by crossed immunoelectrophoresis coupled with separations by rate and isopycnic density gradient centrifugation and by gel exclusion chromatography. Normal rat serum contained distinct lipoprotein species closely analogous to human VLDL, LDL, HDL2 and HDL3. Three days after ligation of the common bile duct, there were major changes in the lipoproteins of rat serum. The amounts of VLDL, LDL and of a minor HDL component were elevated and several novel types of lipoprotein were detected. Three of these could be identified as the characteristic lipoprotein of cholestasis, LP-X, as an enlarged and modified HDL and as a lipoprotein of density 1.055 g/ml intermediate in size between LDL and VLDL. Some unusually small VLDL particles were also detected. It is concluded that the changes in rat serum lipoproteins following ligation of the common bile duct are very similar to the changes observed in cholestatic disease in human patients.     

Diurnal changes in serum triglycerides as related to changes in lipolytic enzymes, (apo) lipoproteins and hormones in normal subjects on a carbohydrate-rich diet

Normal subjects in steady state on a carbohydrate-rich diet (three equivalent meals a day at 9.00, 13.00 and 17.00 h), show a wave-like serum triglyceride (TG) pattern with a peak at 14.00 h. Post-heparin lipoprotein lipase (LPL) activity increased from a mean value of 49 mU/ml +/- 13 (SD) in the fasting state to 127 mU/ml +/- 18 in the fed state (P less than 0.005). This was due to an increase in adipose tissue LPL activity which, at 16.30 and 21.30 h, was significantly higher than basal levels (128.3 +/- 81.5 and 87.7 +/- 23.2 v. 43.3 +/- 9.3 mU/g, P less than 0.05 and P less than 0.01, respectively). Skeletal muscle LPL activity was low (5.8 mU/g +/- 2.3, mean +/- SD) and showed no diurnal change. The observed changes in TG-hydrolysing capacity in the course of the day might explain the TG-pattern. High density lipoprotein (HDL) subfractions HDL2 and HDL3 were separated by density gradient ultracentrifugation and had mean hydrated densities of 1.088 and 1.135 g/ml, respectively. While HDL2 showed no diurnal change, HDL3-cholesterol and-phospholipid significantly increased during the day (P less than 0.005 and P less than 0.001 respectively), reaching their highest levels in the evening. Since te rise in HDL3-lipids follows the fall in serum TG, this provides further indication that the metabolism of these fractions in mutually related.     

Substituting polyunsaturated for saturated fat as a single change in a Swedish diet: effects on serum lipoprotein metabolism and glucose tolerance in patients with hyperlipoproteinaemia

Abstract. A diet with a high content of polyunsaturated fatty acids (PUFA) with a ratio between polyunsaturated and saturated fatty acids (P/S) of 20 and a fat content of 44% was worked out. After an initial 2 weeks' period on a control diet (P/S ratio 0–2) the PUFA diet was fed under isoenergetic conditions at a metabolic ward for 2 weeks to thirty patients with hyperlipoproteinaemia type IIa (n= 7), type IIb (n= 5) and type IV (n=18). The two diets were based on ordinary foodstuff and differed only in regard of the quality of the fat, while the amount of fat as well as the content of other nutrients were kept constant. Compared with the control diet the serum cholesterol concentration decreased by 10%, 13% and 12% on the PUFA diet in patients with hyperlipoproteinaemia type IIa, IIb and IV respectively. In hyperlipoproteinaemia Ila the low density lipoprotein cholesterol decreased by 9% (n.s.) and the high density lipoprotein cholesterol by 16% (P < 005). In hyperlipoproteinaemia type lib the very low density lipoprotein cholesterol decreased by 18% (P < 005), the low density lipoprotein cholesterol by 13% (P < 005) and the high density lipoprotein cholesterol by 5% (n.s.). In type IV the very low density lipoprotein cholesterol decreased by 18% (P < 0–01), the low density lipoprotein cholesterol by 7% (P < 0–05)) while the high density lipoprotein cholesterol remained unchanged. The serum triglyceride concentration decreased by 10% (type IIa), 14% (type lib) and 13% (type IV) on the PUFA diet. The serum concentrations of apolipoprotein A-I and B were reduced by 6% (P < 0–05) and 11% (P < 005) respectively in patients with hyperlipoproteinaemia type IV while the serum apolipoprotein concentration did not change in the patients with hypercholesterolae-mia. Inverse relationships between very low density lipoprotein triglycerides and high density lipoprotein cholesterol were found before treatment (r= 0–49, P < 0–01) which was altered by the treatment (r= 0–28, P > 005). The very low density lipoprotein triglycerides were also found to be inversely related to low density lipoprotein cholesterol both on the control diet (r= -0–65, P < 0001) and the PUFA diet (r= -0–56, P < 001). The regression lines of the latter equations were parallel. The intravenous glucose tolerance was improved (P < 0 05) in patients with hyperlipoproteinaemia type IV on the PUFA diet. The fatty acid composition of the serum lipid esters was significantly changed during the treatment. The relative concentrations of oleic acid and saturated fatty acids decreased while the linoleic acid content increased. The effects of the PUFA diet were less pronounced than the effects of conventional lipid lowering diets where also the fat content has been reduced and where complex carbohydrates have been substituted for simple carbohydrates.     

Changes in acid-base balance following bolus infusion of 20% albumin solution in humans

Objective To evaluate changes in acid-base balance following bolus infusions of a 20% albumin solution.Design and setting Randomized prospective study in a university hospital.Patients and participants Two groups of eight patients each undergoing gynecological surgery.Interventions Patients were randomly assigned to receive either 0.9% saline or lactated Ringers solution. At the end of surgery two boluses of 0.5 g/kg body weight of a 20% albumin solution were administered. Arterial blood gases, electrolytes, and total protein were measured. The strong ion difference and the amount of weak plasma acid were calculated. pH and titratable acidity of the 20% albumin solution were determined.Measurements and results The infusion of a 20% albumin solution resulted in a significant decrease in pH from 7.284 to 7.262 in the saline group and from 7.422 to 7.394 in the Ringers group. In both groups the 20% albumin solution caused an increase in strong ion difference and an increase in the amount of weak plasma acid. The observed changes in serum bicarbonate concentration were in good agreement with the changes in strong ion difference and the amount of weak plasma acid. The 20% albumin solution possessed a pH of 6.95 and a titratable acidity of 85 mEq/l.Conclusions According to the Stewart approach, the observed changes in acid-base balance are the net result of the two opposing effects of the strong ion difference and the amount of weak plasma acid. Alternatively, the acidifying effect of the 20% albumin solution may stem from the titratable acid content of the solution.     

Experimental muscle pain and tenderness following infusion of endogenous substances in humans.

Several human models of myofascial pain exist, but none are similar to clinical pain. The aim of the present study was to develop a clinically relevant model of prolonged human myofascial pain using infusion of the naturally occurring endogenous substances. Initially, bradykinin (Bk), serotonin (5-hydroxytryptamine (5-HT)), histamine (His), prostaglandin E(2) (PGE(2)), adenosine-tri-phosphate (ATP), and their combinations were infused into the trapezius muscle of 36 healthy subjects in a total of 67 sessions to identify substances, which could induce a moderate muscle pain. PGE(2), ATP, and a combination of Bk, 5-HT, His, and PGE(2) produced the intended moderate pain. These substances were further examined in a randomised, blinded, placebo-controlled dose-finding design in 15 healthy subjects in 68 sessions. PGE(2) (3, 6, and 12 nmol/ml) induced mild pain and tenderness not different from placebo. ATP (9000, 18,000, and 36,000 nmol/ml) induced pain of moderate to strong intensity (P=0.04) and the dose of 18,000 nmol/ml furthermore produced moderate local tenderness (P=0.04). Because of unacceptable side effects in subsequent examinations, further studies of ATP in humans were suspended. Infusion of the combination of Bk (92 nmol), 5-HT (156 nmol), His (140 nmol), and PGE(2) (1.95 nmol) produced a moderate pain intensity (P=0.04) and mild tenderness (P=0.04) without inducing unacceptable side effects. Intramuscular infusion of a combination of Bk, 5-HT, His, and PGE(2) induced a prolonged moderate pain and tenderness in healthy humans, and this model may be a valuable tool in future studies of the pathophysiological mechanisms of myofascial pain.     

Distribution and determinants of serum creatinine in the general population: the Hordaland Health Study

Background: Serum creatinine is a well-recognized risk factor for cardiovascular disease (CVD) and is also a rough measure of glomerular filtration rate. The purpose of the present study was to investigate determinants of serum creatinine in the general population. Methods: The participants were recruited as a part of the Hordaland Health Study, and included 6952 men aged 41-49 years, 8218 women aged 41-49 years, 1470 men aged 71-74 years and 1865 women aged 71-74 years. Data on lifestyle factors, medical history and medication were obtained through questionnaires. Body size and blood pressure measurements as well as non-fasting blood samples were obtained during a health examination. Determinants of serum creatinine were identified using multiple linear and logistic regression analyses. Results: Male and older participants had higher levels of serum creatinine than female and middle-aged participants. For older participants, creatinine was associated with serum triglycerides, CVD, upper-arm circumference and use of antihypertensive drugs as well as inversely associated with cigarette smoking. For middle-aged participants, creatinine was associated with upper-arm circumference, serum lipids and physical exercise, as well as inversely associated with smoking and alcohol intake. The associations with CVD risk factors were much stronger for older participants than for middle-aged participants and most associations were significant after adjustments as well as present within the reference range of serum creatinine. Conclusions: In this general population sample, high serum creatinine levels were associated with risk factors for CVD. These associations were stronger in older subjects, whereas in middle-aged subjects lifestyle variables were relatively more important.     

The response of hepatic lipase and serum lipoproteins to acute hyperinsulinaemia in type 2 diabetes

Hepatic lipase has a putative role in the catabolism of HDL particles and, while its activity is dependent upon insulin in the rat, no such insulin responsiveness has been demonstrated in man. We studied 21 patients with type 2 diabetes to examine whether hepatic lipase activity was influenced by hyperinsulinaemia during a 2-4 h isoglycaemic clamp study. Acute changes in lipids, lipoproteins and apolipoproteins were also documented in pre- and post-clamp serum. Hepatic lipase activity during hyperinsulinaemia was compared with activity measured after an equivalent period without insulin. For comparison, nine non-diabetic subjects (matched for age and body mass index) underwent similar clamp studies. In the control experiment without insulin, hepatic lipase activity did not change significantly (mean 9.7 (range 2.3-22.3) in the morning and 9.9 (3.0-22.5) mmol h-1 l-1 in the afternoon, NS). In contrast, after the hyperinsulinaemic clamp, hepatic lipase activity fell significantly in diabetic subjects from 12.8 (4.4-30.6) to 10.4 (3.3-31.3) mmol h-1 l-1, P less than 0.0002 along with serum triglycerides and total and LDL cholesterol. The change in hepatic lipase activity was positively related to the fasting apoprotein B concentration (Spearman r = 0.54, P = 0.016). In the normal subjects, a similar decline in hepatic lipase activity was observed during hyperinsulinaemia (from 15.1 (9.8-32.7) to 12.6 (6.3-28.3) mmol h-1 l-1, P less than 0.01) along with decreases in total, HDL and LDL cholesterol, triglycerides and apoproteins A1 and B.(ABSTRACT TRUNCATED AT 250 WORDS)     

围绝经期和绝经后妇女应用激素替代治疗2年后血脂蛋白和载脂蛋白的变化

目的:探讨结合雌激素并醋酸甲孕酮序贯治疗对围绝经期妇女和绝经期妇女治疗2年后血脂代谢的干预效应。方法:42例围绝经期和绝经期妇女按连续序贯方案每日口服结合雌激素(倍美力)0.625mg,醋酸甲孕酮4mg,连续治疗2年,分别于用药前、用药1年、2年取静脉血测定血脂蛋白、载脂蛋白、雌二醇、促卵泡素水平。结果:用药后总胆固醇、三酰甘油、高密度脂蛋白胆固醇(high-densitylipoproteincholesterol,HDL-C)、载脂蛋白AI、载脂蛋白B、脂蛋白a()较治疗前明显升高,差异有显著性意义(P<0.01)。用药2年后HDL-C水平明显高于用药1年(P<0.05),两组低密度脂蛋白胆固醇(low-densitylipoproteincholesterol,LDL-C无显著性变化。)结论:激素替代治疗有明显调节脂代谢的作用,对心脑血管疾病的发生有一级康复干预作用。     

单纯性肥胖儿童血浆瘦素水平的变化及其与血脂、血糖水平变化的关系

目的 研究单纯性肥胖儿童血清瘦素水平与血糖及血脂、脂蛋白异常的关系。方法 采用放射免疫分析法、酶法对50对7-10岁肥胖及健康对照儿童进行血清瘦素水平及血糖、血脂、脂蛋白水平的测定。结果 单纯性肥胖儿童血清瘦素水平显著高于体重正常组，血清总胆固醇（TC）、甘油三酯（TG）及低密度脂蛋白胆固醇（LDL—C）水平均显著高于体重正常组，血清高密度脂蛋白胆固醇（HDL—C）水平均显著低于体重正常组，轻中度肥胖组血糖水平与对照组无显著性差异（P〉0．05），中度肥胖组血糖水平显著高于对照组儿童（P〈0．05）。血清瘦素水平与体重指数（BMI）、TC、TG、LDL—C、血糖（BS）呈显著正相关关系（P均〈0．05），与血清HDL—C呈显著负相关（P〈0．045）。结论 单纯性肥胖儿童血清瘦素水平显著增高，且与代谢综合征及心血管疾病的危险因素密切相关，可作为筛查高危肥胖儿童的有用指标。     

骨质疏松模型大鼠骨量及血脂的变化

目的观察大鼠去卵巢30,60,90d后骨量及血脂的变化,验证雌激素变化与骨代谢及血脂代谢的时间、变化速度具有相关性的假设成立。方法42只大鼠单纯随机分为两组:假手术组和去卵巢组。分别在实验30,60,90d后处死,取血清及胫骨。观测骨密度(BMD)的变化并检测高密度脂蛋白胆固醇(HDL-C),低密度脂蛋白胆固醇(LDL-C)、总胆固醇(TC)、三酰甘油(TG)。结果大鼠去卵巢后体重增加的速度较快,60d后显著增加,平均为39.5g,比同期假手术组增加19.1g,90d后,同组比较,增加21.1g。去卵巢后,同期去卵巢组BMD均比假手术组减少(P<0.01,t=3.89,9.92,9.52),具有显著性差异,90d同30d相比,BMD从0.287g/cm2下降到0.245g/cm2,仍具有显著性(P<0.01,t=10.38)。30,60d后去卵巢组比同期假手术组LDL-C水平升高(P<0.05,t=2.57,2.46),90d组比较两组无显著性变化。HDL-C在整个实验过程中变化不大。30d组TC,TG水平均显著增加(P<0.01,t=3.48,3.10);60d组同期去卵巢组TC比假手术组增加7.3%(P<0.05,t=2.90),TG增加45.6%(P<0.01,t=3.05);90d组同期去卵巢组TC比假手术组增加6.1%,无统计学意义,TG增加45.6%,各假手术组的TC,TG,LDL-C水平随着时间的增加虽然有所增加,但不具有统计学意义。结论30d去卵巢大鼠已出现典型的骨质疏松表现,伴有血脂紊乱。60,