| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| The influence of estrogen on hepatic cholesterol metabolism and biliary lipid secretion in rats fed fish oil Bravo, E., A. Cantafora, et al. (1999), Biochim Biophys Acta 1437(3): 367-77. Abstract: Both estrogen and dietary n-3 polyunsaturated fatty acids are known to be hypocholesterolemic, but appear to exert their effects by different mechanisms. In this study, the interaction between dietary fish oil (rich in n-3 polyunsaturated fatty acids) and estrogen in the regulation of hepatic cholesterol metabolism and biliary lipid secretion in rats was studied. Rats fed a low fat or a fish oil-supplemented diet for 21 days were injected with 17alpha-ethinyl estradiol (5 mg/kg body weight) or the vehicle only (control rats) once per day for 3 consecutive days. Estrogen-treatment led to a marked reduction in plasma cholesterol levels in fish oil-fed rats, which was greater than that observed with either estrogen or dietary fish oil alone. The expression of mRNA for cholesterol 7alpha-hydroxylase was decreased by estrogen in rats fed a low fat or a fish oil-supplemented diet, while the output of cholesterol (micromol/h/kg b.wt.) in the bile was unchanged in both groups. Cholesterol levels in the liver were increased by estrogen in rats given either diet, but there was a significant shift from cholesterol esterification to cholesteryl ester hydrolysis only in the fish oil-fed animals. Estrogen increased the concentration of cholesterol (micromol/ml) in the bile in rats fed the fish oil, but not the low fat diet. However, the cholesterol saturation index was unaffected. The output and concentration of total bile acid was also unaffected, but changes in the distribution of the individual bile acids were observed with estrogen treatment in both low fat and fish oil-fed groups. These results show that interaction between estrogen-treatment and dietary n-3 polyunsaturated fatty acids causes changes in hepatic cholesterol metabolism and biliary lipid secretion in rats, but does not increase the excretion of cholesterol from the body. |
| The influence of Lactobacillus acidophilus and bacitracin on layer performance of chickens and cholesterol content of plasma and egg yolk Abdulrahim, S. M., S. Y. Haddadin, et al. (1996), Br Poult Sci 37(2): 341-6. Abstract: 1. The influence of Lactobacillus acidophilus alone or in combination with zinc bacitracin on the performance of laying hens was monitored over a period of 4 months. 2. Lactobacillus acidophilus improved egg production, food conversion and reduced the cholesterol concentration in the eggs, but zinc bacitracin had no effect when administered alone. 3. In combination, bacitracin had an adverse effect on the otherwise beneficial activity of the culture. |
| The influence of low amounts of cholesterol on the interdigitated gel phase of hydrated dihexadecylphosphatidylcholine Laggner, P., K. Lohner, et al. (1991), Chem Phys Lipids 60(2): 153-61. Abstract: Dihexadecylphosphatidylcholine (DHPC)/cholesterol binary mixtures in excess of water have been characterized by small-angle X-ray diffraction and differential scanning calorimetry and a temperature-composition phase diagram for this binary has been constructed. The property of cholesterol to perturb the hydrocarbon chain interdigitation in the lamellar gel phase of DHPC and to convert it into a non-interdigitated state has been observed by small- angle X-ray diffraction at cholesterol concentrations as low as 0.1 mol%. The interdigitated and non-interdigitated lamellar gel phases coexist in the range up to 5 mol% cholesterol. At this and higher cholesterol concentrations only non-interdigitated phases have been found in the phase diagram of the mixture. It is suggested that the ability of cholesterol in low concentration to eliminate the hydrocarbon chain interdigitation is related to the free energy increase due to unfavourable line boundaries between the interdigitated and non-interdigitated lipid domains. |
| The influence of membrane cholesterol on the GABAA receptor Bennett, P. J. and M. A. Simmonds (1996), Br J Pharmacol 117(1): 87-92. Abstract: 1. Neurosteroids such as pregnanolone have been established as potent modulators of the GABAA receptor in both electrophysiological and binding studies. Since cholesterol is present in substantial amounts in the neuronal membranes, we have sought evidence for possible interactions of cholesterol with the neurosteroid site and more generally, with the GABAA channel. 2. Synaptosomal membranes were prepared from rat whole brain, cerebral cortex, cerebellum and spinal cord. These membranes were enriched with cholesterol to about double the original level by incubation with liposomes comprised of 50 phosphatidylcholine: 50 cholesterol in the presence of 1% BSA. The additional cholesterol formed a homogeneous mixture with the endogenous cholesterol. 3. The effects of cholesterol and modulatory drugs on the GABAA channel were assessed from the changes induced in 3H-flunitrazepam (FNZ) binding. Cholesterol enrichment did not affect FNZ binding itself; however, the enhancement of 3H-FNZ binding by pregnanolone was affected. In membranes from cerebral cortex, the potency of pregnanolone was reduced by a factor of 3.2 following cholesterol enrichment. By contrast, in membranes from spinal cord, the potency of pregnanolone was increased by a factor of 8.4 following cholesterol enrichment. In membranes from cerebellum, there was little overall change in pregnanolone potency although the effects of threshold concentrations were increased. 4. The enhancement of 3H-FNZ binding by propofol in whole brain membranes was reduced in cholesterol-enriched membranes, similar to the effects of pregnanolone. Experiments with muscimol resulted in an increase in its potency as a potentiator of 3H-FNZ binding, following cholesterol enrichment. 5. These results provide little evidence for a selective competition between cholesterol and pregnanolone at its binding site. Rather, they suggest an influence of membrane cholesterol on the functional coupling between the benzodiazepine site and the other specific drug sites on the GABAA channel. The detailed pattern of influence depended upon the region of CNS and may be related to the subunit composition of the GABAA channels present. |
| The influence of natrium fluoride on serum protein and cholesterol levels in rats with adriblastin-induced nephrotic syndrome Papierkowski, A., M. Jablonski, et al. (1999), Ann Univ Mariae Curie Sklodowska Med 54: 19-23. |
| The influence of neonatal thymectomy on the blood serum level of total lipids, NEFA, triglycerides, total cholesterol and beta-lipoproteins in rats Uzunova, A., D. Strashimirov, et al. (1990), Cor Vasa 32(2): 157-65. Abstract: The time course of changes in the blood serum content of total lipids (TL), nonesterified fatty acids (NEFA), triglycerides (TG), total cholesterol (TC) and beta-lipoproteins (beta-LP), caused by neonatal thymectomy (NTE), was investigated in neonatally thymectomized and in sham-operated rats aged 15, 30, 45 days, 2, 3 and 5 months. TL were significantly increased on days 15, 30, 45 and 60 after operation; their level in 3- and 5-month-old rats was already normal. In control rats, NEFA level increased with age; their level in NTE rats was significantly higher on days 15, 30, 45 and 60 after thymectomy. Similar changes were registered in TG level. The effect of NTE was most pronounced in TC whose level was significantly higher in thymectomized rats than in control rats till the 150th day after operation. Serum concentration of beta-LP in NTE rats exceeded several times that of sham-operated rats in all age groups. The role of the thymus in the control of lipid metabolism in rats is discussed. |
| The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials. Harvard Atherosclerosis Reversibility Project Research Group Sacks, F. M., C. M. Gibson, et al. (1995), Am J Cardiol 76(9): 78C-85C. Abstract: Angiographic trials of coronary atherosclerosis treatment have demonstrated that lowering low density lipoprotein (LDL) cholesterol concentrations improves coronary artery stenosis. Most patients in previous trials have had at least mildly elevated LDL. Recently, however, the Harvard Atherosclerosis Reversibility Project (HARP) did not find such benefit in patients with lower baseline LDL levels compared with previous trials. We reviewed and analyzed all cholesterol-lowering trials that used angiographic endpoints. Unifactorial trials of hypocholesterolemic dietary or drug therapy demonstrated that the higher the baseline LDL, the greater the improvement in quantitatively determined stenosis in the treatment group compared with the controls (r =.83). Considering the change in stenosis in the treatment group alone, regression was more common in trials in which baseline mean LDL was > 170 mg/dl (> 4.4 mmol/liter), whereas progression occurred when baseline mean LDL was < 170 mg/dl (< 4.4 mmol/liter). HARP had the lowest baseline LDL (137 mg/dl 3.54 mmol/liter), and showed no tendency for improvement in lesions. In contrast to the influence of baseline LDL levels, neither a low LDL level achieved on treatment nor a large percentage reduction in LDL was related to improvement in lesions. Sample size differences between HARP and the other trials are unlikely to be a major explanatory factor, since trials of comparable sample size to HARP, but with higher initial LDL, demonstrated favorable results. We conclude that coronary lesions that develop in the context of average LDL levels show less angiographic improvement in response to substantial LDL reduction than lesions in hypercholesterolemic patients.(ABSTRACT TRUNCATED AT 250 WORDS) |
| The influence of size and composition on the cholesterol mobilizing properties of liposomes in vivo Rodrigueza, W. V., P. H. Pritchard, et al. (1993), Biochim Biophys Acta 1153(1): 9-19. Abstract: As part of a study into the antiatherogenic properties of phospholipid liposomes we have investigated the capacity of a variety of preparations to increase plasma cholesterol concentrations in mice. Large unilamellar vesicles, composed of egg phosphatidylcholine, were found to be approximately twice as effective at mobilizing cholesterol than sonicated vesicles of the same composition. For egg phosphatidylcholine liposomes the change in plasma cholesterol profile is proportional to the residence time of vesicles in the circulation. Large unilamellar vesicles with a diameter of approx. 100 nm accumulate the most sterol in the animal model tested here, reaching equimolar concentrations with phospholipid after 24 h. Gel-state vesicles gave rise to a smaller increase in plasma cholesterol compared to liquid-crystalline vesicles. Our data indicate that, in vivo, net transfer of cholesterol into liposomes occurs more extensively from the lipoprotein cholesterol pool than from the erythrocyte cell membrane pool. This is consistent with the hypothesis (Williams, K.J., Werth, V.P. and Wolff, J.A. (1984) Perspect. Biol. Med. 27, 417-431) that liposomes enhance reverse cholesterol transport by generating cholesterol-poor HDL particles that can extravasate and promote more sterol efflux from peripheral tissues. |
| The influence of the acyl-CoA:cholesterol acyltransferase-1 gene (-77G-->A) polymorphisms on plasma lipid and apolipoprotein levels in normolipidemic and hyperlipidemic subjects Ohta, T., K. Takata, et al. (2004), Biochim Biophys Acta 1682(1-3): 56-62. Abstract: BACKGROUND: Acyl-CoA:cholesterol acyltransferase (ACAT) plays important roles in cellular cholesterol homeostasis. Two isoforms of ACAT have been reported (ACAT-1 and ACAT-2). ACAT inhibitors cannot only prevent atherosclerosis formation, but may also induce its regression in animals. In humans, an ACAT inhibitor was shown to have a lipid-lowering effect. The present study was carried out to clarify the relationship between ACAT-1 gene variants and hyperlipidemia. METHODS AND RESULTS: To identify genetic variants, we screened 30 subjects with hyperlipidemia by direct sequencing. As a result, a missense variant (R526G) and a variant in the 5' untranslated region (-77G-->A) were identified. The genotype frequencies of each variant were determined in 178 unrelated normolipidemic and 441 unrelated hyperlipidemic subjects. The alleles frequencies of the R526G variant in normolipidemic and hyperlipidemic subjects were 0.676 and 0.633, respectively. The alleles frequencies of the -77G-->A variant in normolipidemic and hyperlipidemic subjects were 0.503 and 0.515, respectively. Differences in allele frequencies between normolipidemic and hyperlipidemic subjects were not significant in both variants. R526G variant did not affect plasma concentrations of lipids or apolipoproteins in subjects studied. However, among hyperlipidemic subjects, plasma concentrations of HDL-C and apoA-I in subjects with -77G-->A variant were significantly higher than those in subjects without variant. CONCLUSION: Two variants in ACAT-1 gene were identified in subjects with hyperlipidemia. -77G-->A variant affects plasma HDL concentrations only in hyperlipidemic subjects. These data suggest that the intracellular FC concentration might modulate plasma HDL concentrations. |
| The influence of the incorporation of cholesterol and water on the particle size, bilayer thickness, melting behavior, and relative sucrose ester composition of reversed vesicles Mollee, H. M., D. P. Steenvoorden, et al. (2001), J Pharm Sci 90(5): 588-98. Abstract: The influence of the incorporation of cholesterol and water on the particle size, bilayer thickness, melting behavior, and relative sucrose ester composition of reversed vesicles was studied. Reversed vesicles (RVs) were prepared of sucrose ester in silicon oil by sonication. The RVs were characterized by polarized light microscopy, laser diffraction, high-performance liquid chromatography, small angle X-ray scattering (SAXS), and differential scanning calorimetry. The particle size distributions of the studied dispersions were bimodal with peaks at 5 and 0.4 microm. There was no significant difference in the sucrose ester composition of these two size categories of RVs. The incorporation of cholesterol and water had no effect on the size distribution of the RVs. The SAXS results showed that the RVs prepared without cholesterol and water consisted of bilayers with fully interdigitated alkyl chains. The incorporation of high concentrations of cholesterol caused a phase separation within the bilayers. The incorporation of water also resulted in a phase separation within the bilayers but at a lower cholesterol concentration. The presence of two different size classes of RVs in one RVs dispersion and the phase separation within the bilayers of certain compositions can have consequences for the application of RVs. |
| The influenza virus ion channel and maturation cofactor M2 is a cholesterol-binding protein Schroeder, C., H. Heider, et al. (2005), Eur Biophys J 34(1): 52-66. Abstract: The influenza-virus M2 protein has proton channel activity required for virus uncoating and maturation of hemagglutinin (HA) through low-pH compartments. The proton channel is cytotoxic in heterologous expression systems and can be blocked with rimantadine. In an independent, rimantadine-resistant function, M2, interacting with the M1 protein, controls the shape of virus particles. These bud from cholesterol-rich membrane rafts where viral glycoproteins and matrix (M1)/RNP complexes assemble. We demonstrate that M2 preparations from influenza virus-infected cells and from a baculovirus expression system contain 0.5-0.9 molecules of cholesterol per monomer. Sequence analyses of the membrane-proximal M2 endodomain reveal interfacial hydrophobicity, a cholesterol-binding motif first identified in peripheral benzodiazepine receptor and human immunodeficiency virus gp41, and an overlapping phosphatidylinositol 4,5-bisphosphate-binding motif. M2 induced rimantadine-reversible cytotoxicity in intrinsically cholesterol-free E. coli, and purified E. coli-expressed M2 functionally reconstituted into cholesterol-free liposomes supported rimantadine-sensitive proton translocation. Therefore, cholesterol was nonessential for M2 ion-channel function and cytotoxicity and for the effect of rimantadine. Only about 5-8% of both M2 preparations, regardless of cholesterol content, associated with detergent-resistant membranes. Cholesterol affinity and palmitoylation, in combination with a short transmembrane segment suggest M2 is a peripheral raft protein. Preference for the raft/non-raft interface may determine colocalization with HA during apical transport, the low level of M2 incorporated into the viral envelope and its undisclosed role in virus budding for which a model is presented. M2 may promote clustering and merger of rafts and the pinching-off (fission) of virus particles. |
| The inhibition of cholesterol esterification by cyclandelate in transformed mouse macrophages Heffron, F., B. Middleton, et al. (1993), Biochem Pharmacol 45(9): 1829-34. Abstract: Cyclandelate (trimethylcyclohexanyl mandelate) inhibited cholesterol esterification in a transformed mouse macrophage cell line (J774) with a concentration of approximately 20 microM being required for half-maximal inhibition. The intact drug was required for its inhibitory action since neither of its hydrolysis products, trimethylcyclohexanol and mandelic acid, caused any inhibition even at high concentrations. The drug entered the cells very rapidly with inhibition being apparent within the shortest time possible to measure esterification (15 min after drug addition). The rate of cholesterol esterification returned to control values when drug-inhibited cells were incubated in drug-free medium indicating a rapid loss of drug from the cells. Loading of cells with cholesterol had no effect on the inhibitory action of cyclandelate, and the inhibition of esterification of cholesterol appeared to be specific, since the syntheses of phospholipid and triacylglycerol (which also involve the action of acyltransferases) were not affected by the drug. Similar inhibitions of cholesterol esterification were seen in four other cell lines, a human osteosarcoma, Chinese hamster ovary cells, a human transformed macrophage cell line (U937) and human umbilical cord vein endothelial cells, as well as in slices of pig aorta, indicating a general action in extra-hepatic tissues where the drug is not hydrolysed. |
| The inhibition of the human cholesterol 7alpha-hydroxylase gene (CYP7A1) promoter by fibrates in cultured cells is mediated via the liver x receptor alpha and peroxisome proliferator-activated receptor alpha heterodimer Gbaguidi, G. F. and L. B. Agellon (2004), Nucleic Acids Res 32(3): 1113-21. Abstract: In previous work, we showed that the binding of the liver x receptor alpha:peroxisome proliferator-activated receptor alpha (LXRalpha:PPARalpha) heterodimer to the murine Cyp7a1 gene promoter antagonizes the stimulatory effect of their respective ligands. In this study, we determined if LXRalpha:PPARalpha can also regulate human CYP7A1 gene promoter activity. Co-expression of LXRalpha and PPARalpha in McArdle RH7777 hepatoma cells decreased the activity of the human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol. In vitro, the human CYP7A1 Site I bound LXRalpha:PPARalpha, although with substantially less affinity compared with the murine Cyp7a1 Site I. The binding of LXRalpha:PPARalpha to human CYP7A1 Site I was increased in the presence of either LXRalpha or PPARalpha ligands. In HepG2 hepatoblastoma cells, fibrates and 25-hydroxycholesterol inhibited the expression of the endogenous CYP7A1 gene as well as the human CYP7A1 gene promoter when co-transfected with plasmids encoding LXRalpha and PPARalpha. However, a derivative of the human CYP7A1 gene promoter that contains a mutant form of Site I that does not bind LXRalpha:PPARalpha was not inhibited by WY 14,643 or 25-hydroxycholesterol in both McArdle RH7777 and HepG2 cells. The ligand-dependent recruitment of LXRalpha:PPARalpha heterodimer onto the human CYP7A1 Site I can explain the inhibition of the human CYP7A1 gene promoter in response to fibrates and 25-hydroxycholesterol. |
| The inhibitory effect of a novel antiatheromatous agent, E5050, on the intimal thickening of aorta in cholesterol-fed rabbit in vivo Saeki, T., I. Ohtsuka, et al. (1991), Jpn J Pharmacol 56(2): 159-66. Abstract: The development of atheromatous lesions in the aortic arch of 0.5% cholesterol-fed rabbits was biochemically and morphologically examined. The animals were killed at week twelve (Cont-12W) or sixteen (Cont-16W). Both the micrographic and biochemical studies showed that the main atheromatous lesions in the Cont-12W group were fatty streaks, whereas those in the Cont-16W group were fibrous plaques. In these models, oral ingestion of 0.2% and 0.4% E5050, which has an antiproliferative effect on smooth muscle cells, had no effect on the surface involvement or the lipid content of the aortic arch at the sixteenth week, but reduced the degree of intimal thickening and the DNA content in the aortic arch in a dose-dependent manner. These results strongly suggest that E5050 suppresses the intimal thickening through its inhibitory effect on the proliferation of smooth muscle cells. |
| The inhibitory effects of dai-chai-hu-tang (dai-saiko-to) extract on supersaturated bile formation in cholesterol gallstone disease Shoda, J., Y. Matsuzaki, et al. (1996), Am J Gastroenterol 91(4): 828-30. |
| The ins and outs of reverse cholesterol transport Groen, A. K., R. P. Oude Elferink, et al. (2004), Ann Med 36(2): 135-45. Abstract: It is generally assumed that HDL is the obligate transport vehicle for 'reverse cholesterol transport', the pathway for removal of excess cholesterol from peripheral tissues via the liver into bile and subsequent excretion via the feces. During the last few years, intensive research has generated exciting new data on the separate processes involved in reverse cholesterol transport. Many 'new' proteins, particularly members of the ABC transporter and nuclear receptor subfamilies, that mediate or influence cholesterol fluxes have been identified and characterized. An important role of the intestine in regulation of cholesterol homeostasis is emerging. In this paper, new insights into mechanisms of reverse cholesterol are reviewed. |
| The insulin, glucose and cholesterol level and activity of lysosomal enzymes in the course of the model alloxan diabetes Witek, B., T. Krol, et al. (2001), Neuro Endocrinol Lett 22(4): 238-42. Abstract: OBJECTIVES: The study was carried out on fifty male rabbits of the New Zealand White breed. Diabetes was caused by a single, intravenous alloxan injection. Rabbits which had glycaemia 7th day after the alloxan administration higher than 11 millimol/litre were selected for the studies. They were divided into 5 groups: I - control (without diabetes); II - 3-week diabetes; III - 6-week diabetes; IV - 3-month diabetes; V - 6-month diabetes. METHODS: In control and experimental rabbits the activity of beta-glucuronidase, N-acetyl-beta-glucosaminidase, lysosomal acid phosphatase, leucine aminopeptidase, cathepsin D, and lysosomal arylesterase was determined in lysosomal fractions of the liver and kidney. RESULTS: Alloxan caused lowering of the activity of all the investigated enzymes in the kidney and liver except lysosomal arylesterase. CONCLUSION: Alloxan injection caused a significant increase in the activity of all the investigated enzymes. The advisable lysosomal enzymes may be useful for the monitoring of the course and effectiveness of diabetes therapy. |
| The integrity of a cholesterol-binding pocket in Niemann-Pick C2 protein is necessary to control lysosome cholesterol levels Ko, D. C., J. Binkley, et al. (2003), Proc Natl Acad Sci U S A 100(5): 2518-25. Abstract: The neurodegenerative disease Niemann-Pick Type C2 (NPC2) results from mutations in the NPC2 (HE1) gene that cause abnormally high cholesterol accumulation in cells. We find that purified NPC2, a secreted soluble protein, binds cholesterol specifically with a much higher affinity (K(d) = 30-50 nM) than previously reported. Genetic and biochemical studies identified single amino acid changes that prevent both cholesterol binding and the restoration of normal cholesterol levels in mutant cells. The amino acids that affect cholesterol binding surround a hydrophobic pocket in the NPC2 protein structure, identifying a candidate sterol-binding location. On the basis of evolutionary analysis and mutagenesis, three other regions of the NPC2 protein emerged as important, including one required for efficient secretion. |
| The integrity of cholesterol-enriched microdomains is essential for the constitutive high activity of protein kinase B in tumour cells Elhyany, S., E. Assa-Kunik, et al. (2004), Biochem Soc Trans 32(Pt 5): 837-9. Abstract: A deregulated activity of PKB/Akt (where PKB stands for protein kinase B) renders tumour cells resistant to a variety of apoptosis-inducing stimuli. Elucidation of the mechanisms responsible for this deregulation is of prime importance for the development of novel anti-cancer drugs. Results of the present study demonstrate that the constitutive activity of PKB/Akt in B16BL6 melanoma cells depends on the integrity of cholesterol-enriched membrane microdomains, since the exposure of cells to cholesterol-depleting agents decreases the phosphorylation of this enzyme, with no change in its total protein level. Inhibitors of Hsp90 (heat-shock protein 90) decreased phosphorylation of PKB/Akt with a similar pattern. Dephosphorylation of the enzyme, as a consequence of raft disintegration, could be precluded by inhibition of serine/threonine (but not tyrosine) phosphatases. Our results imply that destabilization of lipid rafts seemingly affects the association of Hsp90 with the respective serine/threonine phosphatases, thereby increasing the accessibility to PKB/Akt to deactivating phosphatases. We have found recently that reconstituted expression of H-2K class I glycoproteins in class I-deficient B16BL6 cells also decreases the phosphorylation of PKB/Akt. Therefore it is possible that raft-associated regulation of this important enzyme involves both H-2K glycoproteins and Hsp90. |
| The interaction of dietary cholesterol and specific fatty acids in the regulation of LDL receptor activity and plasma LDL-cholesterol concentrations Dietschy, J. M., L. A. Woollett, et al. (1993), Ann N Y Acad Sci 676: 11-26. Abstract: From these brief considerations, it is clear that the steady-state LDL-cholesterol concentration is determined in a powerful way by the interaction of dietary cholesterol and specific fatty acids. There appear to be only a few saturated fatty acids and an even lesser number of unsaturated fatty acids that significantly interact with cholesterol in the liver cell to alter hepatic LDL receptor activity. These effects are uniformly seen in most experimental animals and in humans under circumstances where the experiments are properly designed. Future work is urgently needed to define the metabolic effects of the more unusual fatty acids (e.g., the trans fatty acid) and the more intimate details of how these substances regulate LDL receptor activity in the cell. It is also of considerable importance to extend these studies to the members of the same species that exhibit variable responses to these same dietary lipids. It is now clear that the magnitude of these specific responses to dietary cholesterol and specific fatty acids varies in different individuals with different genetic backgrounds from the same species. Elucidating the reasons for this variability is another area of research of considerable importance to human biology. |