Biomedical subjects
Publications and source records attributed to H Lithell.
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Nine hyperlipoproteinaemic patients were treated with a serum lipid-lowering diet during 4 weeks in a metabolic ward. The diet contained 35% energy from fat and the ratio between polyunsaturated and saturated fats (the P/S ratio) was 2.0. This treatment caused a reduction of the serum concentrations of the low density lipoprotein cholesterol (Chol) by 17% (P less than 0.01), of the apolipoprotein (apo) B by 27% (P less than 0.01), of high density lipoprotein (HDL) Chol by 15% (P less than 0.05) and of the apo A-I by 9% (P less than 0.02). The apo B/apo A-I ratio decreased by 19% (P less than 0.01). It is suggested that the reduced HLD Chol and apo A-I concentrations may be due to both the qualitative change to more polyunsaturated fats in the diet and to the reduction of the total dietary fat intake.
The fatty acid composition of the plasma lipid esters has been studied during lipid-lowering treatment of 95 patients with atherosclerotic disease. During the first two months of the trial only a diet was prescribed. During the ensuing two months either clofibrate or niceritrol, a nicotinic acid ester, was added in a randomized order. During the last two months the second drug was added. The combined treatment with diet, clofibrate and niceritrol caused highly significant serum lipid reductions. The fatty acid composition in the plasma lipid esters was determined in samples from each trial period to measure the degree of dietary adherence. During dietary treatment the relative content of saturated and monounsaturated fatty acids secreased and the polyunsaturated fatty acids increased with an increasing ratio between pulyunsaturated and saturated fatty acids (P/S ratio) in the cholesterol esters and triglycerides. Only minor changes were seen in the phospholipids. The changes caused by the diet were partly reversed by clofibrate while niceritrol did not cause any major changes of the fatty acid composition. Clofibrate treatment coincided with increasing amounts of monounsaturated fatty acids, especially oleate (18 : 1), in the cholesterol esters, triglycerides and phospholipids while there were significant reductions of the content of linoleic (18 : 2) acid in both the cholesterol esters and triglycerides. The 18 : 2/18 : 1 ratio decreased significantly in all the lipid esters analyzed. However, the P/S ratio was not significantly affected, partly because the relative content of saturated fatty acids also tended to decrease during clofibrate treatment. It is concluded that addition of clofibrate treatment to patients who are on a diet enriched with polyunsaturated fats is associated with a change from polyunsaturated to monounsaturated fatty acids in the plasma lipid esters but does not significantly effect the ratio between polyunsaturated and saturated fatty acids. The fatty acid changes caused by clofibrate treatment and counteracted by an increased amount of polyunsaturated fat in the diet.
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Previous studies have demonstrated an inverse relationship between plasma high density lipoproteins (HDL) cholesterol and coronary heart disease risk. In the present study we investigated prospectively the effect of a moderate physical conditioning programme on plasma lipids and lipoproteins, especially HDL-cholesterol and apolipoprotein A-I (apo A-I), the major apoprotein of HDL. Healthy, sedentary, middle-aged men were randomly selected and assigned either to a training group (n = 24, age 40 +/- 3.4, mean +/- SD) or to a control group (n = 13, age 39 +/- 5.0). Training consisted of various indoor and outdoor sports activities 45 min/day, 3 times/week for 12 weeks at an intensity of approximately 80% of measured maximal oxygen uptake (VO2 max). The trained subjects were studied at 4, 8 and 12 weeks. The training increased VO2 max by 12% (P less than 0.01). Increases were observed in both apo A-I (10%, P less than 0.02) and HDL-cholesterol (8%, P less than 0.02) after training, with significant increases already after 4 and 8 weeks, respectively. Furthermore, decreases in total plasma cholesterol (5%, P less than 0.004) and plasma triglycerides (26%, P less than 0.003) were found without changes in body weight, body composition, cigarette smoking, alcohol consumption or the percentage composition of dietary intake. Fasting serum-insulin concentrations decreased significantly during training. No changes were noted in the control group. The present study demonstrates prospectively that moderate physical training can increase HDL.
A health examination survey comprising 2 322 men born in 1920-24 was carried out in 1970-73 at the University Hospital, Uppsala. Untreated subjects with a diastolic BP greater than or equal to 105 mmHg and those already on treatment for hypertension were considered hypertensives. If a BP elevation was verified at a second screening and the patient had no established contact with a physician, he was offered treatment. Thus, 83 men have been followed up for at least 6 years. The overall reduction in SBP after 6 years was 29.0 mmHg and in DBP 19.6 mmHg. Six men have died, four of them from myocardial infarction, five have dropped out for other reasons. The percentage of non-responders (DBP greater than or equal to 105 mmHg) 1, 2, 3, 4 and 5 years +/- 3 months after the start of treatment was high, about 20% on the average. On the other hand, when the mean BP for the non-responders at all visits to the hypertension clinic was compared with their pretreatment value, a reduction of 29.3 mmHg in SBP and 17.0 mmHg in DBP was achieved. The results with regard to compliance and BP reduction are encouraging and would seem to justify more widespread screening and treatment.
The feasibility of reducing serum lipoprotein levels in patients with atherosclerotic disease by combining diet, clofibrate and nicotinic acid (niceritrol) has been investigated. An additive lipid-lowering effect of diet and the two drugs was demonstrated. It was possible to reduce the serum triglycerides (TG) in hypertriglyceridaemic patients by 50-60%. This corresponded to a reduction of very low density lipoprotein (VLDL) TG by 73 and 66% in patients with hyperlipoproteinaemia (HLP) type IIB and IV, respectively. In normotriglyceridaemic patients the serum TG concentration decreased by 30-40%. The serum cholesterol (Chol) concentration was reduced by 33% and the low density lipoprotein (LDL) Chol by 37% in HLP type IIA and IIB. The LDL Chol decreased by 32% in normolipoproteinaemic patients and by 21% in HLP type IV. The mean value for serum cholesterol after therapy was in all groups close to 200 mg/100 ml. In hypertriglyceridaemic patients high density lipoprotein (HDL) Chol increased by 18%. Clofibrate and niceritrol differed with regard to the effect on serum lipoprotein concentrations as well as on other metabolic parameters. Niceritrol was significantly more effective than clofibrate in lowering LDL Chol and in increasing HDL Chol. Niceritrol treatment significantly reduced the Chol/TG ratio in VLDL while no such effect was seen during clofibrate administration. The two drugs also showed significantly different effects on the fractional removal rate (K2) of triglyceride-rich lipoproteins as measured by the intravenous fat tolerance test (IVFTT). The K2 was significantly increased by clofibrate but was not affected by niceritrol treatment. The two drugs differed also with regard to the effects on serum uric acid concentration and the liver function tests. The plasma fibrinogen levels and the erythrocyte sedimentation rates were reduced during treatment with both niceritrol and clofibrate. The present study demonstrates that it is possible to obtain substantial reductions of serum lipoprotein concentrations by combining lipid-lowering diet, clofibrate and niceritrol treatment. There was an additive lipid-lowering effect of this treatment and the combination of the two drugs seemed beneficial in regard to certain possible side effects. The impact of a lipid reduction within this range on cardiovascular morbidity and mortality remains to be evaluated.
Seven young, healthy subjects performed bicycle exercise with a working load leading to exhaustion after one hour of work. The tests were done in the afternoon in the fed state. The serum insulin concentrations decreased from 22 to 4 mU/l and plasma glucagon increased from 241 to 340 pg/l already after 30 min of work. The level of adipose tissue lipoprotein lipase activity (LPLA) did not fall as had been expected, but increased. The skeletal muscle LPLA was unchanged. The results indicate that during the first hour of heavy exercise the heparin-releasable LPLA in tissues is not influenced by the work induced changes in serum hormone levels.
Lipoprotein-lipase (LPL) activity and intracellularly stored triglycerides were determined in muscle biopsies taken before and after an 85 km skiing race from 7 volunteers. The triglyceride stores were larger in slow twitch than in fast twitch fibres (proportions 5:1 before the race). The LPL activity increased and the triglyceride stores in slow twitch fibres decreased during the race. The best trained subjects had the largest TG stores before the race and their TG stores also decreased most during the race. These subjects also had very small increase of LPL activity. The least trained subject on the other hand showed a 6-fold increase of LPL activity. The high post-race LPL activity in less trained subjects indicates a higher capacity for uptake of fatty acids from serum TG as compared to the more trained subjects.
An in vitro assay system was developed for the determination of lipoprotein-lipase activity in 10--30-mg specimens of human skeletal muscle tissue. The reaction medium of the assay was based on a glycine buffer of pH 8.3 (at 37 degrees C) with a heparin concentration of 1.5 g/l (about 180 IU/ml). The enzyme activity was measured as the release of [3H]oleic acid from a serum-activated, triglyceride emulsion, in which [3H]trioleate was used as trace substance. The enzyme activity studied had the characteristic properties of lipoprotein-lipase activity, i.e. it was activated by the addition of serum or apolipoprotein C-II and inhibited in the presence of high ionic strength, protamine sulphate or apolipoprotein C-III. A mean Km of 0.40 +/- 0.13 (S.D.) mmol/l for triglyceride substrate was found in tissue samples that had very different concentrations of lipoprotein-lipase activity. This Km was similar to the low fasting concentrations of very low density lipoprotein triglycerides often found in healthy individuals. The lipoprotein-lipase activity was not decreased freezing and storing the tissue specimens in liquid nitrogen. The within-day variation of the method was 16 percent and the between-day variation 8 percent. Muscle tissue from the vastus lateralis muscle had, on the average, a 60 percent higher concentration of lipoprotein-lipase activity than the rectus abdominis muscle in the same subject.
The capacity of para-aminosalicylic acid (PAS) to lower initially high serum lipoprotein lipid concentrations was tested in a double-blind crossover study. Thirty patients who were on a lipid-lowering diet were treated with PAS (6 gm daily) for 4 wk. There was an average reduction of the serum triglyceride concentration of 28% (p less than 0.001) and of 12% of the serum cholesterol concentration (p less than 0.001) corresponding to a reduction of very low density lipoprotein (VLDL) triglycerides of 40% (p less than 0.001) and low density lipoprotein (LDL) cholesterol of 6% (p less than 0.05). In hypercholesterolemic patients, the LDL cholesterol reduction was 14% (p less than 0.001). In patients with hypertriglyceridemia type IV, the mean reduction of the VLDL triglyceride concentration was 47% (p less than 0.01), corresponding to a serum triglyceride reduction by 37% (p less than 0.01). In spite of the decrease of VLDL concentration, there was an unexpected reduction of the lipoprotein lipase activity in adipose tissue of 16% (p less than 0.02). The glucose tolerance and the serum insulin concentrations at fasting and after glucose injection were not changed.
Sixteen healthy subjects, 7 females and 9 males, with a mean age of 25 years (range 22--29 years), were studied in the fasting state in the morning and 8 h later after partaking of breakfast, lunch and two small meals. The lipoprotein-lipase activity in the adipose tissue increased significantly from 80 +/- 32 to 117 +/- 61 nmol fatty acid released per gram and minute (nmol FA/g/min), whereas in skeletal-muscle tissue it decreased significantly from 25 +/- 11 to 17 +/- 9 nmol FA/g/min. The concentration of serum triglycerides increased significantly from 0.93 +/- 0.18 mmol/l (mean +/- SD) in the fasting state to 1.57 +/- 0.64 mmol/l in the fed state. In the fasting state the lipoprotein-lipase activity of skeletal muscle was inversely related to the ratio between the concentrations of insulin and glucagon.
1. Post-heparin lipolytic activity in man has been studied by using a triglyceride substrate emulsion containing different emulsifiers. 2. The lipolytic activity measured was profoundly influenced by the type of emulsifier used in the substrate. Substrate stabilized by synthetic emulsifiers give higher lipolytic activity than Intralipid, which contains egg phospholipids as emulsifiers. This difference was solely explained by higher salt-resistant lipase activities found with emulsions containing synthetic emulsifiers. The salt-inhibited lipase activity, which has properties as a lipoprotein lipase, was not influenced by the type of emulsifier. 3. When used under specified conditions Intralipid seems to be virtually specific for extrahepatic post-heparin lipolytic activity.
Lipoprotein-lipase activity was determined in tissue from the skeletal muscle of the leg and the subcutaneous adipose tissue of the abdomen in fourteen patients before and after 1 month of clofibrate administration. The concentrations of serum triglycerides decreased by, on the average, 37% in a group of thirteen patients which mainly consisted of subjects with type-IV hyperlipoproteinaemia. Clofibrate administration was associated with an average increase of the skeletal muscle-tissue lipoprotein-lipase activity of 50% (P less than 0.005). There was a significant correlation between the percentage changes in skeletal muscle-tissue lipoprotein-lipase activity and those of the triglycerides concentrations and the K2-values in an intravenous fat tolerance test during clofibrate treatment. Adipose-tissue lipoprotein-lipase activity did not change significantly. One patient with type-I hyperlipoproteinaemia had very low values of skeletal muscle-tissue lipoprotein-lipase activity and moderately low adipose-tissue lipoprotein-lipase activity. In this patient, neither the tissue lipoprotein-lipase activity nor the triglycerides concentration changed during clofibrate therapy. Fasting serum insulin concentrations decreased significantly during clofibrate administration and the percentage decrease was significantly correlated to the percentage increase of skeletal-muscle lipoprotein-lipase activity. It is suggested that the lowering of insulin levels is a possible mechanism through which glucagon activity is enhanced and this may increase skeletal muscle-tissue lipoprotein-lipase activity.
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The lipoprotein-lipase activity (LPLA) in the abdominal, subcutaneous, adipose tissue was studied in a random sample (n = 69) of 60-year-old men. A new method for the quantification of LPLA was applied. The mean value was 67 mU/g when expressed per gram (wet weight) of adipose tissue. Several subjects within the lower part of the range of adipose-tissue LPLA values had low concentrations of serum-triglycerides (S-TG). There was no correlation between the LPLA and S-TG concentrations in the fasting state. Among the 69 subjects, four had newly detected diabetes mellitus and had significantly lower LPLA in the adipose tissue than the control group. The fat-cell size and the LPLA per gram of adipose tissue were not correlated. Thus, obesity without diabetes mellitus does not imply a low LPLA concentration in adipose tissue. The variation of the concentration of adipose-tissue LPLA in the fasting state in this population was explained only to a minor extent by the variation of S-insulin and blood-glucose parameters, when analysed statistically by a stepwise multiple-regression technique.
The lipoprotein-lipase activities (LPLA) and fat cell sizes were determined in subcutaneous, adipose tissue from four different sites in a group of 17 obese women. The LPLA per gram and per cell were significantly higher in the adipose tissue from gluteal and femoral sites than in tissue from the abdominal site. The degree of obesity of the subjects, as reflected in the fat cell size, was correlated with the LPLA per cell, so that large cells contained more LPLA per cell than small cells. On the other hand, no correlation was found between the cell size and the LPLA per gram. Intra-individually, the cell weight was related also to the LPLA per gram, so that sites with large fat cells also had high concentrations of LPLA per gram. The interpretation of the results with regard to obesity and to the variation in size of fat depots in an individual is discussed.
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