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Homozygosity for the apolipoprotein (apo) E variant apoE2(158 Arg----Cys) invariably gives rise to dysbetalipoproteinemia, and when associated with obesity or a gene for hyperlipidemia, results in type III hyperlipoproteinemia. The association of the E2/2 phenotype with type IV/V hyperlipoproteinemia rather than type III hyperlipoproteinemia in identical twin brothers led us to investigate the primary structure of their apoE. Lipoprotein electrophoresis on agarose gels confirmed the presence of increased very low density lipoproteins (VLDL) and chylomicrons but little, if any, beta-VLDL, indicating that these subjects did not have dysbetalipoproteinemia. When the apoE from these twins was subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis on a system that can distinguish apoE2(158 Arg----Cys) from all other known apoE variants, it gave rise to two components. One had the unique mobility of apoE2(158 Arg----Cys), and one migrated in the position of the other variants of apoE (and normal apoE3), indicating that the brothers were heterozygous for apoE2(158 Arg----Cys) and a second apoE2 isoform. Cysteamine modification and isoelectric focusing showed that, like apoE2(158 Arg----Cys), the second apoE2 isoform also contained two cysteine residues. The structural mutation in the second apoE2 isoform was determined by peptide sequencing. Like normal apoE3, this variant had arginine at position 158, but differed from apoE3 by the substitution of cysteine for arginine at position 228. Total apoE isolated from the brothers had the same receptor-binding activity in a competitive binding assay as a 1:1 mixture of normal apoE3 and apoE2(158 Arg----Cys).(ABSTRACT TRUNCATED AT 250 WORDS)

Lecithin:cholesterol acyltransferase (LCAT) activity, lipid concentration, lipoprotein lipid concentrations and cholesteryl ester linoleic acid proportion were determined in the plasma of 85 subjects randomly selected from a population during a health screen survey. Mean fractional LCAT rate was significantly higher in men than in women. Molar LCAT rate correlated with low density lipoprotein (LDL) cholesterol concentration in men and with nearly all lipoprotein lipid concentrations in women. Most of these relationships were dependent on plasma unesterified cholesterol (UC) concentration. Fractional LCAT rate was correlated only with HDL cholesterol concentration in women and this relation was dependent on the influence of obesity. An inverse relationship between plasma cholesteryl ester (PCE) linoleic acid proportion and molar LCAT rate in women was also explained by influences of obesity on the data. Both fractional and molar LCAT rates were positively correlated with obesity (Quetelet's Index and subscapular skinfold thickness) in women but not in men. This study showed the influence of sex on nearly all correlations involving LCAT activity in combined groups of men and women.

Indices of obesity, plasma lipids, and lipoprotein levels, plasma cholesteryl ester fatty acid composition, reported alcohol consumption and smoking habits were measured in 88 men and 87 women, ages over 15 years, randomly selected from the total respondents (1192) to a health survey. Most indices of obesity were related to plasma triglycerides and high-density lipoprotein levels in both sexes; to very low-density lipoprotein levels in men only; and to plasma cholesteryl ester fatty acid linoleic acid proportions in women only. The correlations with high-density lipoprotein cholesterol levels were dependent on very low-density lipoprotein triglyceride levels in men but not in women. Indices of obesity were significantly higher in nonsmoking women and reported alcohol consumption correlated with Quetelet's index (body mass index) in men. Smoking habits, but not alcohol consumption, influenced correlations between indices of obesity and plasma triglycerides and very low-density lipoprotein triglyceride levels in men. The present results showed several sex-related differences in relationships with indices of obesity. Lower very low-density lipoprotein levels, higher skinfold measurements, higher cholesteryl ester fatty acid linoleic acid proportions and lower alcohol intake in women than in men may be responsible. The data suggested that in women, altered diet composition may be linked with obesity.

The effect of linoleic acid on the induction of fatal ventricular fibrillation by intravenous CaCl2 (10%), was studied in rats fed for a month from weaning on a diet with either a high or low content of linoleic acid. Studies were performed in the basal state and after pretreatment with noradrenaline, which increased the sensitivity to CaCl2 equally in animals from both diet groups. Despite considerable differences in the linoleic acid levels in the plasma and myocardium, the two groups did not differ in the incidence of fatal ventricular fibrillation. Our conclusions concerning the effect of linoleic acid on cardiac arrhythmias, and sudden death in particular, are compared with those from other studies.

In epididymal adipose tissue from rats, human serum antagonizes inhibition of basal lipolysis by nicotinic acid in vitro. Under similar conditions caffeine-stimulated lipolysis was unaffected by the presence of human serum. Very low density (VLDL), low density (LDL) and high density (HDL) lipoproteins were all found to antagonize the action of nicotinic acid on basal lipolysis. VLDL also antagonized prostaglandin E1 (PGE1)-inhibition of basal lipolysis in vitro. The fat cell membrane was suggested as the site at which human serum lipoproteins antagonize nicotinic acid or PGE1 antilipolytic action on basal lipolysis in vitro.

Seventeen previously sedentary men (aged 30-45) were exercised approximately twice weekly over a 10-week period during which time there was a significant fall in low density lipoprotein cholesterol, but total high density lipoprotein (HDL) did not change. The subfraction HDL2 showed an initial fall at two weeks of training with a subsequent rise above the baseline by 10 weeks. HDL3 cholesterol tended to change in an opposite direction to HDL2 thus accounting for no significant change in total HDL cholesterol. Smoking or drinking habits did not change throughout the study. As body weights did not change significantly through the study, energy intake must have increased with probable increased very low density lipoprotein (VLDL) production. Loss of apoprotein C-peptides from HDL2 associated with activation of lipoprotein lipase, and clearance of VLDL, could have caused redistribution of C-apoproteins between HDL3 leading to the changes seen, with the establishment of a new equilibrium with continued training by 10 weeks.

Three diets, consisting respectively of formulations high in oleic and stearic acid, linolenic acid, and lauric acid, were fed to rats until the adipose tissue TGFA largely reflected the dietary pattern of fatty acids. The composition of the serum FFA under basal conditions and following noradrenaline-stimulated lipolysis, were examined in relation to the respective adipose tissue TGFA. It was found in both in vivo and in vitro studies that lauric acid appeared to be less easily mobilized than longer chain acids. The in vitro studies indicated that this could not be explained either by positional preference of the shorter chain acids for the alpha-position of esterification or by increased reesterification of the shorter chain acids. The possibility remains that the difference is due to some specificity of tissue lipases for certain ester linkages.

The effects of nicotinic acid on plasma free fatty acid levels and turnover and on plasma glycerol levels were studied in the first few hours after administration to man and the sheep. In both species a fall in all parameters studied was followed by a rise above basal level, interpreted as due to an increase in lipolysis above resting level. The significance of the findings is discussed.