Lars A. Carlson

Determination of glycerides in blood serum.

Abstract A method has been presented for the estimation of the serum glycerides. The basic principle is the determination of the glycerol part of the glycerides after separation of the phospholipids on silicic acid. The method is discussed and compared with earlier methods for the estimation of the glycerides in blood serum.

Metabolism of triglyceride-rich lipoproteins during alimentary lipemia.

The metabolism of chylomicron remnants and VLDL was studied in healthy controls and normo- (NTG) and hypertriglyceridemic (HTG) patients with coronary artery disease after intake of an oral fat load. Specific determination of apo B-48 and B-100 enabled separation of the respective contribution of the two lipoprotein species. The postprandial plasma levels of small (Sf 20-60) and large (Sf 60-400) chylomicron remnants increased in controls and NTG patients. In contrast, only large chylomicron remnants increased in the HTG patients. An increase of large VLDL was seen in response to the oral fat load in all groups, whereas small VLDL were either unchanged in the controls and the NTG patients, or decreased in the HTG patient group. The whole plasma concentration of C apolipoproteins was essentially uninfluenced by the oral fat load, whereas the content in large triglyceride-rich lipoproteins paralleled the apo B elevations in controls and NTG patients. An even more prominent increase of apo B in large triglyceride-rich lipoproteins in the HTG group was not accompanied by an increase of C apolipoproteins. These findings indicate that chylomicrons compete with VLDL for removal of triglycerides by lipoprotein lipase and that the postprandial metabolism of triglyceride-rich lipoproteins is severely defective in hypertriglyceridemia.

Unresponsiveness to the lipid mobilizing action of catecholamines in vivo and in vitro in the domestic fowl

Abstract In the anesthetized domestic fowl, continous infusion of norepinephrine caused a significant rise in the systolic blood pressure. On the other hand, no significant effect was observed on the concentration of the free fatty acids of plasma. Mesenteric adipose tissue from hens, cocks and rats were incubated in vitro and the effect of various agents on the lipolysis, measured as glycerol release, was studied. While 0.5μg. of norepinephrine per ml. caused a maximal stimulation with a seven-fold increase in glycerol release on rat adipose tissue, a dose of 10μg. per ml. had no significant effect on fowl adipose tissue. Fowl adipose tissue, in contrast to rat adipose tissue, was also unresponsive to porcine ACTH. On the other hand, glucagon stimulated the glycerol release from fowl and rat adipose tissue to a similar extent.

Changing relative proportions of apolipoproteins CII and CIII of very low density lipoproteins in hypertriglyceridaemia

The very low density lipoproteins (VLDL) of fasting serum from subjects with normo- and hypertriglyceridaemia (Type IV and V) were separated into subfractions by density gradient centrifugation. The tetramethylurea (TMU)- soluble apolipoproteins were separated by polyacrylamide gel electrophoresis and the relative proportions of apo CII and CIIIs determined. There were highly significant correlations between the concentration of VLDL triglycerides and apo CII (r---0.92), apo CIII1 (r=+0.88) and the ratio apo CII/apo CIII1 (r= --0.94). It was suggested that the decreasing ratio apo CII/CIII1 with increasing triglyceride levels might cause a resistance to lipoprotein lipase and therefore a defect lipolysis of VLDL based upon a changed ratio apo CII/apo CII1 might be part of the pathogenesis of the hypertriglyceridaemia.

Concentration of triglycerides, phospholipids and glycogen in skeletal muscle and of free fatty acids and beta-hydroxybutyric acid in blood in man in response to exercise.

Twenty‐four fasting male subjects exercised until exhaustion on a bicycle at a relative workload of about 70% of the workload at heart rate 170 per min. Muscle tissue was obtained by needle biopsy from the lateral femoral muscle before and after exercise.—The average work time was 99 min. The muscle triglyceride concentration decreased during the exercise from 10.4 to 7.8 μmoles per gram and that of glycogen from 10.4 to 3.4 mg per gram. The concentration of phospholipids in the muscle remained unchanged.‐The amount of fatty acids and of glucose which were oxidized during the exercise was calculated from the oxygen uptake and the respiratory quotient and found to be 39 % and 61 % respectively of the caloric output. It was estimated that the muscle triglyceride and plasma free fatty acids (FFA) contributed about 2/3 and 1/3 respectively of the fatty acids oxidized. Similar calculations showed that muscle glycogen covered about 2/3 of the amount of glucose oxidized.—A number of correlation coefficients were calculated between the various parameters studied. There was no correlation between the triglyceride and glycogen content of the muscle. The amount of work performed was correlated to the glycogen (r = 0.60) and to the triglyceride (r = − 0.53) content of the muscle. These two muscle substrates could be used to predict the work performance by multiple linear regression analysis with an error of only 17 % and with a multiple correlation coefficient of 0.774.—The work performance was positively correlated to the amount of fatty acids oxidized but negatively correlated to the decrease in muscle triglycerides which suggests that the capacity to perform aerobic work is related to the utilization and mobilization of fatty acids from extramuscular sources.The obvious importance of local tissue stores of substrate such as glycogen and triglycerides for the energy metabolism was discussed.

Studies on the Relation between Mobilization of Free Fatty Acids and Energy Metabolism in Man : Effects of Norepinephrine and Nicotinic Acid

Abstract The magnitude of the increase in oxygen consumption produced by intravenously infused 1-norepinephrine in fasting young men was well correlated with the increase it produced in plasma level of free fatty acids. The calorigenic effect of norepinephrine was partially inhibited by prior injection of nicotinic acid in quantities sufficient to prevent its fat-mobilizing action. These findings, coupled with the failure of nicotinic acid to affect discernably the effects of norepinephrine on carbohydrate metabolism and cardiovascular and respiratory functions, support the concept that the calorigenic effect of norepinephrine results, in part, from mobilization and oxidation of free fatty acids derived from adipose tissue. Basal energy metabolism was not altered when plasma levels of free fatty acids were reduced by injections of nicotinic acid, but the respiratory quotient rose significantly. These observations suggest that the level of oxidative metabolism is not influenced appreciably in resting adult human subjects by the availability of free fatty acids as fuel and are compatible with the hypothesis that oxidation of carbohydrate is inhibited by utilization of free fatty acids in man.

Serum triglycerides, to be or not to be a risk factor for ischaemic heart disease?

The Stockholm Prospective Study--in a 14.5 year follow-up of 3486 men--found plasma triglycerides but not plasma cholesterol to be an independent risk factor for ischaemic heart disease. This finding stands in sharp contrast to the opposite results of the 8.5 year follow-up of the Western Collaborative Group Study. Differences between the two studies are discussed as one way of explaining the varying results--the most important probably being the use of different end-points for the diagnosis of ischaemic heart disease, but geographical, environmental and ethnic differences may also be of importance.

Effect of combined clofibrate-nicotinic acid treatment in ischemic heart disease. An interim report.

Abstract Over a three and a half year period beginning in December 1972, 555 survivors of myocardial infarction (442 men and 113 women) under the age of 70 years were recruited from one hospital for a therapeutic trial aimed to reduce serum lipids and to study the effect on subsequent morbidity and mortality. Following a stabilization period of 3 months after infarction, patients were given a dietary program to reduce serum lipids. Patients were then randomly divided into (a) a treatment group which received a combined regimen of nicotinic acid (up to 3 g daily) and 2 g of clofibrate daily, and (b) a control group on diet alone. By April 1979, 59 and 57 patients in the control and drug-treated groups respectively had completed 5 years in the trial. In the same respective groups, 101 and 99 patients continued in the study. In comparison with the control group serum cholesterol and triglycerides showed mean falls of 14 and 19% respectively in the drug-treated group over the 5-year period. During the trial there were 39 and 25 IHD deaths in the control and drug-treated groups respectively ( P = 0.06). Further mortality in the year after leaving the trial brought the totals to 53 and 31 IHD deaths ( P Non-fatal infarcts occurred at rates of 4.6 and 2.5 ( P P

Effect of nicotinic acid on plasma lipids in patients with hyperlipoproteinemia during the first week of treatment

Summary Thirteen patients with hyperlipoproteinemia were treated with nicotinic acid. The fasting plasma lipid level was followed before treatment and daily during the first 5 days of treatment with 1 g of nicotinic acid three times a day. After treatment for 1 day the average triglyceride level was significantly reduced, whilst the cholesterol concentration was unaffected. The triglycerides then remained fairly stable at this new level. The cholesterol level, however, was not significantly reduced until the 4th and 5th days of treatment. The concentration of phospholipids behaved in a similar way to that of cholesterol. These findings suggest that the concentration of the triglyceride-rich very low density lipoproteins (VLDLP) is reduced after 1 days treatment, whereas the level of the cholesterol and phospholipid-rich low density lipoproteins (LDLP) is not lowered until the 4th to 5th days. This type of lipoprotein change was confirmed by analysis of plasma lipoproteins, separated in the preparative ultracentrifuge, from a case of essential hypercholesterolemia. The following working hypothesis for the action of nicotinic acid on plasma lipids is suggested. Nicotinic acid inhibits mobilization of free fatty acids from adipose tissue. This reduces the uptake of free fatty acids in the liver, which is followed in turn by decreased hepatic formation of VLDLP. The consequences would be reduced conversion of VLDLP to LDLP and, eventually, diminution of the LDLP level in plasma; thus plasma cholesterol and phospholipids would be lowered. Further work is required to confirm this hypothesis and to determine whether nicotinic acid has other effects on fatty acid transport than that of inhibiting lipolysis in adipose tissue.

Effect of BM 15.075 on lipoprotein concentrations in different types of hyperlipoproteinaemia

The four-week lipoprotein lowering effect of 0.2 g t.i.d. of BM 15.075 and of 0.5 g t.i.d. of clofibrate was studied in 29 subjects with different types of hyperlipoproteinaemia in a single blind crossover fashion. BM 15.075 decreased very low density lipoproteins (VLDL), triglycerides (TG) and cholesterol concentration in all types of hyperlipoproteinaemia the effect being dependent on initial lipoprotein concentrations. BM 15.075 decreased VLDL triglyceride concentrations on average 20% more than did clofibrate. BM 15.075 decreased low density lipoproteins (LDL) cholesterol concentrations in Type IIA and IIB but did not significantly affect this lipoprotein lipid in type IV hyperlipoproteinaemia. Regression analysis showed that the drug tended to decrease LDL cholesterol if initial concentrations were above 157 mg/100 ml and to increase initially lower levels. No significant differences between BM 15.075 and clofibrate was found in the effect of LDL cholesterol. High density lipoproteins (HDL) cholesterol concentrations were not influenced by BM 15.075. No subjective side effects were noted on BM 15.075. S-ASAT increased and alcaline phosphatases decreased on both treatments.