- Email: [email protected]
Trans fatty acids and lipoproteins
Monday IO October 1994: Workshop Abstracts W6 Nutrition, lipoproteins and atherosclerosis
87
W6 NUTRITION, LIPOPROTEINS AND ATHEROSCLEROSIS Trans fatty acids and lipoproteins
m,
Mensink RP, van To1 A*, Zock PL, Dept. of Human
Nutrition, Anricultural Univ., Bomenwen 2. 6703 HD Waneningen; *Dept. >f Biochem., Erasmus Univ.: Rotterdam, The Netherlands
Isomeric fatty acids are unsaturated fatty acids with one or more double bonds in an unusual configuration (trans instead of cis) or position (positional cis isomers). The term trans is loosely used to refer to both types. Trans fatty acids arise through biohydrogenation in the rumen of cows and sheep or catalytic hydrogenation in oil-processing factories. The effects of trans monounsaturates on lipoproteins in man are opposite to those of the natural cis acid, oleic acid. Our own experiments in healthy volunteers employed 11% or 7.5% of energy as trans in strictly controlled diets. Trans fatty acids raised LDL and Lp(a) and lowered HDL, all in dosedependent fashion; raised serum cholesteryl ester transfer activity in 52/55 volunteers (mean change 18%, p < 0.02) and significantly lowered the HDL ratio of cholesteryl esters to triglycerides. LCAT was unchanged. Thus, trans fatty acids raise LDL, lower HDL and raise Lp(a) in man. The effects on HDL and LDL may be mediated through CETP. Effect of monounsaturated fatty acids on lipoprotein metabolism Jacotot, Sola R, Service Mddecine Inteme 5, HGpital Henri Mondor, 94010 Cretei CJdex, France
The increased consumption of monounsaturated fatty acids (MUFA) is associated with a low incidence of cardiovascular diseases, but the mechanisms of this relation are unclear. We investigated the role of dietary MUFA on the reverse transport of cholesterol mediated by HDL3 and on the subsequent regulation of intracellular cholesterol homeostasis. The study revealed that HDL3 obtained from the subjects fed the MUFA diet (compared with saturated or polyunsaturated fats diet) induced the highest [3H]free cholesterol efflux from cultured tibroblasts coupled with a reduced content of intracellular cholesterol and a higher LDL receptor activity in the cells. These variations of cholesterol efflux appear to be the consequence of modifications of HDW physicochemical parameters, particularly of HDW phospholipid fatty acid composition, fluidity and size. In conclusion, dietary fats induce physicochemical changes in HDW that can modulate cellular cholesterol metabolism. Sola et al. Arteriosclerosis Thrombosis 1993; 13: 958-966. Dietary cholesterol and plasma lipoproteins wPJ, CSIRO Division of Human Nutrition, PO Box 10041, Gouger Street, Adelaide SA 5000, Australia
It is not clear whether dietary cholesterol (DCh) directly contributes to coronary heart disease or only by influencing the lipoprotein profile. In specific situations DCh raises cholesterol in LDL, HDh and VLDUIDL. However the variability in responses is a classic example of genetic and nutritional factors interacting. The more desirable rise in HDb rather than in LDL occurs more in women, in younger people, in those with low LDL and in people with low waist-hip ratios (female fat distribution). Maleness, age and raised LDL predispose to a rise in LDL with DCh. One effect of the square root relationship between dietary and plasma cholesterol is that the effect of change in DCh is less when intake is high than when it is low, thus obscuring an effect at current ‘Western’ intakes. We have found good reproducibility in individuals. We have not found an effect of background dietary fatty acid profile on
response to DCh; but others have. While apo E genotype influences response to DCh (highest with E4), we have not found an effect of apo B gene polymorphism @co Rl or Xbal); in studies where this has been shown, the polymorphism accounts for a low percentage of LDL variability. Although diminished hepatic LDL receptor function has not been shown directly in humans, this is a likely major effect of DCh. Increased lipoprotein production has also been demonstrated for IDL and LDL. Changed hepatic lipase and lipid transfer protein activities may contribute to the HDb cholesterol rise. Compensatory responses involving cholesterol metabolism (decreased synthesis and increased excretion of ster01s) are well documented. It may become possible and certainly desirable to identify people whose genetic makeup predisposes them to DCh-induced hypercholesterolemia. Such improved targeting strengthens public health recommendations. Genetic factors in lipoprotein responsiveness to diet Schaefer EJ, Ordovas JM, Lichtenstein AH, Lipid Metabolism Lab., USDA Human Nutrition Research Center on Aging at Tufts Univ., Boston, MA, USA
The only common mutations within the population known to affect lipoprotein metabolism are apo E and apo A-N isoforms. Apo E2 differs from apo E3 by having a cysteine instead of an arginine at residue 158, while apo E4 differs from apo E3 by having an arginine at residue 112 instead of a cysteine. In participants in the Framingham Offspring Study that have had apo E isoforms assessed (n = 2258) the allele frequencies of epsilon 2, 3 and 4 were 0.08, 0.79 and 0.13, respectively. These alleles accounted for 1.0% of the variability in LDL-C in men, 0.5% in premenopausal women, and 5.0% in post-menopausal women. Apo A-IV-2 differs from apo A-IV-l by having a histidine instead of a glutamine at residue 360. The allele frequencies of apo A-N1 and apo A-IV-2 in the population are approximately 0.9 and 0.1, respectively, with the latter allele being associated with somewhat higher HDL-C levels in some studies. We studied LDL-C lowering in response to diets restricted in total fat (<30%), saturated fat (
Dietary saturated fatty acids and cholesterol, both individually and together, decrease LDL receptor activity in the liver. This impairs LDL removal from the plasma and hence increases plasma LDL concentrations. The capacity of a food or diet to affect plasma LDL concentration can be. denoted by a single number, the cholesterol saturated fat index (CSI). Fruits, grains, beans
Atherosclerosis X, Montreal, October I994
87
W6 NUTRITION, LIPOPROTEINS AND ATHEROSCLEROSIS Trans fatty acids and lipoproteins
m,
Mensink RP, van To1 A*, Zock PL, Dept. of Human
Nutrition, Anricultural Univ., Bomenwen 2. 6703 HD Waneningen; *Dept. >f Biochem., Erasmus Univ.: Rotterdam, The Netherlands
Isomeric fatty acids are unsaturated fatty acids with one or more double bonds in an unusual configuration (trans instead of cis) or position (positional cis isomers). The term trans is loosely used to refer to both types. Trans fatty acids arise through biohydrogenation in the rumen of cows and sheep or catalytic hydrogenation in oil-processing factories. The effects of trans monounsaturates on lipoproteins in man are opposite to those of the natural cis acid, oleic acid. Our own experiments in healthy volunteers employed 11% or 7.5% of energy as trans in strictly controlled diets. Trans fatty acids raised LDL and Lp(a) and lowered HDL, all in dosedependent fashion; raised serum cholesteryl ester transfer activity in 52/55 volunteers (mean change 18%, p < 0.02) and significantly lowered the HDL ratio of cholesteryl esters to triglycerides. LCAT was unchanged. Thus, trans fatty acids raise LDL, lower HDL and raise Lp(a) in man. The effects on HDL and LDL may be mediated through CETP. Effect of monounsaturated fatty acids on lipoprotein metabolism Jacotot, Sola R, Service Mddecine Inteme 5, HGpital Henri Mondor, 94010 Cretei CJdex, France
The increased consumption of monounsaturated fatty acids (MUFA) is associated with a low incidence of cardiovascular diseases, but the mechanisms of this relation are unclear. We investigated the role of dietary MUFA on the reverse transport of cholesterol mediated by HDL3 and on the subsequent regulation of intracellular cholesterol homeostasis. The study revealed that HDL3 obtained from the subjects fed the MUFA diet (compared with saturated or polyunsaturated fats diet) induced the highest [3H]free cholesterol efflux from cultured tibroblasts coupled with a reduced content of intracellular cholesterol and a higher LDL receptor activity in the cells. These variations of cholesterol efflux appear to be the consequence of modifications of HDW physicochemical parameters, particularly of HDW phospholipid fatty acid composition, fluidity and size. In conclusion, dietary fats induce physicochemical changes in HDW that can modulate cellular cholesterol metabolism. Sola et al. Arteriosclerosis Thrombosis 1993; 13: 958-966. Dietary cholesterol and plasma lipoproteins wPJ, CSIRO Division of Human Nutrition, PO Box 10041, Gouger Street, Adelaide SA 5000, Australia
It is not clear whether dietary cholesterol (DCh) directly contributes to coronary heart disease or only by influencing the lipoprotein profile. In specific situations DCh raises cholesterol in LDL, HDh and VLDUIDL. However the variability in responses is a classic example of genetic and nutritional factors interacting. The more desirable rise in HDb rather than in LDL occurs more in women, in younger people, in those with low LDL and in people with low waist-hip ratios (female fat distribution). Maleness, age and raised LDL predispose to a rise in LDL with DCh. One effect of the square root relationship between dietary and plasma cholesterol is that the effect of change in DCh is less when intake is high than when it is low, thus obscuring an effect at current ‘Western’ intakes. We have found good reproducibility in individuals. We have not found an effect of background dietary fatty acid profile on
response to DCh; but others have. While apo E genotype influences response to DCh (highest with E4), we have not found an effect of apo B gene polymorphism @co Rl or Xbal); in studies where this has been shown, the polymorphism accounts for a low percentage of LDL variability. Although diminished hepatic LDL receptor function has not been shown directly in humans, this is a likely major effect of DCh. Increased lipoprotein production has also been demonstrated for IDL and LDL. Changed hepatic lipase and lipid transfer protein activities may contribute to the HDb cholesterol rise. Compensatory responses involving cholesterol metabolism (decreased synthesis and increased excretion of ster01s) are well documented. It may become possible and certainly desirable to identify people whose genetic makeup predisposes them to DCh-induced hypercholesterolemia. Such improved targeting strengthens public health recommendations. Genetic factors in lipoprotein responsiveness to diet Schaefer EJ, Ordovas JM, Lichtenstein AH, Lipid Metabolism Lab., USDA Human Nutrition Research Center on Aging at Tufts Univ., Boston, MA, USA
The only common mutations within the population known to affect lipoprotein metabolism are apo E and apo A-N isoforms. Apo E2 differs from apo E3 by having a cysteine instead of an arginine at residue 158, while apo E4 differs from apo E3 by having an arginine at residue 112 instead of a cysteine. In participants in the Framingham Offspring Study that have had apo E isoforms assessed (n = 2258) the allele frequencies of epsilon 2, 3 and 4 were 0.08, 0.79 and 0.13, respectively. These alleles accounted for 1.0% of the variability in LDL-C in men, 0.5% in premenopausal women, and 5.0% in post-menopausal women. Apo A-IV-2 differs from apo A-IV-l by having a histidine instead of a glutamine at residue 360. The allele frequencies of apo A-N1 and apo A-IV-2 in the population are approximately 0.9 and 0.1, respectively, with the latter allele being associated with somewhat higher HDL-C levels in some studies. We studied LDL-C lowering in response to diets restricted in total fat (<30%), saturated fat (
Dietary saturated fatty acids and cholesterol, both individually and together, decrease LDL receptor activity in the liver. This impairs LDL removal from the plasma and hence increases plasma LDL concentrations. The capacity of a food or diet to affect plasma LDL concentration can be. denoted by a single number, the cholesterol saturated fat index (CSI). Fruits, grains, beans
Atherosclerosis X, Montreal, October I994