| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Growth hormone (GH) treatment decreases postprandial remnant-like particle cholesterol concentration and improves endothelial function in adult-onset GH deficiency Twickler, T. B., H. W. Wilmink, et al. (2000), J Clin Endocrinol Metab 85(12): 4683-9. Abstract: Premature atherosclerosis is a clinical feature in adult-onset GH deficiency. Evidence is accumulating that disturbances in triglyceride metabolism, reflected by abnormalities in circulating remnant lipoproteins, are associated with increased atherogenic potential. In a case-controlled intervention study, we investigated postprandial lipoprotein metabolism using a new remnant lipoprotein method based on immunoseparation principle RLP-cholesterol (RLP-C). In addition, we analyzed retinyl ester (RE) analysis in plasma and in Sf < 1000 fraction. Endothelial function was assessed as flow-mediated dilatation (FMD). Eight patients diagnosed with acquired adult-onset GH deficiency and eight controls matched for gender, age, body mass index, and apolipoprotein (apo) E genotype were enrolled in the study. Oral vitamin A fat loading tests were performed at baseline in both groups and after 6 months of treatment with recombinant human GH (rh-GH) in the adult-onset GH-deficient patients. Adult-onset GH-deficient patients had significantly higher fasting RLP-C, postprandial RLP-C concentrations (plasma RLP-C, 0.29 +/- 0.14 mmol/L; and incremental area under the curve-RLP-C, 2.13 +/- 1.60 mmol*h/L, respectively) than controls (0.19 +/- 0.06 mmol/L and 1.05 +/- 0.72 mmol*h/L (P: < 0.05), respectively). They also had significantly higher postprandial RE in plasma and Sf < 1000 fraction. Treatment with rh-GH significantly reduced postprandial RLP-C concentrations (incremental area under the curve-RPL-C 0.73 +/- 0.34 mmol*h/L; P: < 0.05) but had no effects on the fasting RLP-C concentrations (0.317 +/- 0.09 mmol/L, P: < 0.05), or on the postprandial RE in plasma and in Sf < 1000 fraction. Endothelial function measured as FMD was improved from 5.9 +/- 3.3% to 10.2 +/- 4.0% (P: < 0.05) in patients treated with rh-GH. It is concluded that patients with adult-onset GH deficiency have increased levels of fasting and postprandial RLP-C and an impaired endothelial function as measured as FMD. Treatment with rh-GH resulted in a decrease of postprandial RLP-C concentration, thereby improving the postprandial atherogenic lipoprotein profile and improvement of endothelial function, however, the clearance of large chylomicron particles as reflected by RE remained disturbed. |
| Growth hormone and bile acid synthesis. Key role for the activity of hepatic microsomal cholesterol 7alpha-hydroxylase in the rat Rudling, M., P. Parini, et al. (1997), J Clin Invest 99(9): 2239-45. Abstract: Growth hormone (GH) has an important role in the regulation of hepatic LDL receptor expression and plasma lipoprotein levels. This investigation was undertaken to characterize the effects of GH on hepatic cholesterol and bile acid metabolism in the rat. In hypophysectomized (Hx) rats, the activities of the rate-limiting enzymes in cholesterol and bile acid biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and cholesterol 7alpha-hydroxylase (C7alphaOH), were reduced by 71 and 64%, respectively. HMG CoA reductase mRNA levels were reduced by 37%, whereas C7alphaOH mRNA was increased by 81%. LDL receptor expression was reduced by 18% in Hx rats, without any change in the LDL receptor mRNA levels. Although the normal diurnal variation of C7alphaOH activity was preserved in Hx rats, the activity of C7alphaOH was much reduced both at midday and midnight. Total hepatic cholesterol was increased by 14% in Hx animals whereas microsomal cholesterol was unchanged. The rate of cholesterol esterification was enhanced (by 38%) in liver microsomes from Hx rats. Stepwise hormonal substitution of Hx rats showed that GH, but not thyroid hormone or cortisone, was essential to normalize the enzymatic activity of C7alphaOH. GH also normalized the altered plasma lipoprotein pattern in Hx rats, and increased the fecal output of bile acids. The latter effect was particularly evident when GH was combined with cortisone and thyroid hormone. Also in normal rats, GH stimulated C7alphaOH activity. In conclusion, GH has an essential role to maintain a normal enzymatic activity of C7alphaOH, and this, at least in part, explains the effects of GH on hepatic cholesterol metabolism. GH is also of critical importance to normalize the altered plasma lipoprotein pattern in Hx rats. |
| Growth hormone and its effects on cholesterol and lipoprotein metabolism following surgical intervention (hGH and cholesterol metabolism during surgery) Martin, R., M. D. Cano, et al. (1998), Nutr Hosp 13(4): 181-5. Abstract: The objective of this work was to determine whether the increase in serum GH, IGF1, glucose and insulin levels caused by the administration of hGH modifies the normal response of cholesterol and lipoproteins to surgical aggression. A prospective, randomized, and double blind study is carried out in 28 patients operated for gallstones and diverticulitis. The control group (n = 15) was not given anything except conventional fluidtherapy in the postoperative period: the patients in the hGH (n = 13) group were also given 8 IU of hGH during the first five days after the intervention. The comparative study of the triglycerides, cholesterol, LDLc, HDL-c, and A-1 B apolipoproteins shows that in the group treated with hGH the normal response of cholesterol and lipoproteins to surgical aggression is attenuated. |
| Growth hormone receptor variant (L526I) modifies plasma HDL cholesterol phenotype in familial hypercholesterolemia: intra-familial association study in an eight-generation hyperlipidemic kindred Takada, D., Y. Ezura, et al. (2003), Am J Med Genet A 121(2): 136-40. Abstract: Defect of growth hormone receptor (GHR) is classically known to cause Laron syndrome, characterized by short stature, specific facial appearance, elevated serum growth hormone levels, and decreased insulin-like growth factor I levels. In addition, an increased cardiovascular risk due to elevated plasma total and LDL cholesterol levels marks another feature of the disease. Growth hormone (GH) plays an important role in the regulation of lipoprotein metabolism. GH status was found to be an independent determinant of plasma total cholesterol and triglyceride levels in humans. We studied a total of 207 members of eight-generation extended family of familial hypercholesterolemia (FH) in which affected members presented with various lipoprotein phenotypes. Intra-familial correlation analysis of a modifier effect of a Leu526Ile substitution in GHR gene was carried out among 95 carriers for LDL receptor gene (LDLR) mutation and 112 non-carriers. When plasma high-density lipoprotein cholesterol (HDL-c) levels in the LDLR-mutation carriers were compared, a significant lowering effect of HDL-c was observed with the Leu allele; the values were lowest among Leu/Leu homozygotes (mean +/- SD = 37 +/- 2 mg/dl), highest in Ile/Ile homozygotes (50 +/- 4 mg/dl), and intermediate among Leu/Ile heterozygotes (41 +/- 2 mg/dl) (P = 0.0021). The results indicate a significant modification of the phenotype of FH with the defective LDLR allele, by GHR Leu variation in the kindred studied. |
| Growth hormone reduces plasma cholesterol in LDL receptor-deficient mice Rudling, M. and B. Angelin (2001), Faseb J 15(8): 1350-6. Abstract: Growth hormone (GH) has pleiotropic effects on cholesterol and lipoprotein metabolism. Pituitary GH is important for the normal regulation of hepatic LDL receptors (LDLR), for the enzymatic activity of bile acid regulatory cholesterol 7alpha-hydroxylase (C7alphaOH), and for the maintenance of resistance to dietary cholesterol. The present study aimed to determine whether GH has beneficial effects on plasma lipids and hepatic cholesterol metabolism in mice devoid of LDLR. Compared with wild-type controls, LDLR-deficient mice had approximately 250% elevated plasma total cholesterol and approximately 50% increased hepatic cholesterol levels; hepatic HMG CoA reductase activity was reduced by 70%, whereas C7alphaOH activity was increased by 40%. In LDLR mice, GH infusion reduced plasma cholesterol and triglycerides up to 40%, whereas HMG CoA reductase and C7alphaOH activities were stimulated by approximately 50% and 110% respectively. GH also stimulated HMG CoA reductase and C7alphaOH activities in control mice, whereas hepatic LDLR and plasma lipoproteins were unchanged. The effects of cholestyramine and atorvastatin on C7alphaOH in LDLR-deficient mice were potentiated by GH, and this was associated with a further reduction in plasma cholesterol. GH treatment reduces plasma cholesterol and triglycerides and stimulates C7alphaOH activity in mice devoid of LDLR, particularly in combination with resin or statin treatment. The potential of GH therapy in patients with homozygous familial hypercholesterolemia should be evaluated. |
| Growth hormone selectively improves intestinal cholesterol absorption after jejunoileal autotransplantation in pigs Pakarinen, M. P., P. Pirinen, et al. (2004), J Pediatr Surg 39(8): 1220-5. Abstract: BACKGROUND/PURPOSE: Small bowel transplantation impairs enteric function and causes malabsorption of cholesterol and bile acids. Growth hormone stimulates intestinal absorptive function. The authors hypothesized that long-term growth hormone therapy could improve absorption of bile acids and cholesterol after autotransplantation of the jejunoileum. METHODS: Sixteen pigs with similar food, cholesterol, and fat intake underwent either sham laparotomy or a model of jejunoileal autotransplantation, including extrinsic autonomic denervation, lymphatic interruption, and in situ cold ischemia. Five randomly chosen autotransplanted animals received daily growth hormone treatment for 8 weeks. Serum lipids, absorption, and excretion of cholesterol, bile acids, and fat were determined after 8 weeks. Mucosal morphometrics, proliferation, and enzyme activities were determined. Plasma cholesterol precursors and plant sterols, respective markers of cholesterol synthesis and absorption, were measured after 2 and 8 weeks. RESULTS: After jejunoileal autotransplantation, growth hormone treatment significantly increased body weight gain, cholesterol absorption efficiency from 45.1% to 62.1%, plasma campesterol to cholesterol proportions, and biliary secretion of cholesterol. With or without growth hormone treatment, autotransplantation significantly increased fecal bile acid excretion, plasma cholesterol precursors, fecal bacterially modified neutral sterols, mucosal thickness of the ileum (but not jejunum), and intestinal transit time when compared with sham-operated animals. Crypt cell proliferation, mucosal enzyme activities, and microvilli showed no differences between the groups. CONCLUSIONS: These findings suggest that growth hormone treatment selectively improves cholesterol, but not bile acid absorption, after autotransplantation of the jejunoileum. |
| Growth hormone treatment of growth hormone-deficient adults results in a marked increase in Lp(a) and HDL cholesterol concentrations Eden, S., O. Wiklund, et al. (1993), Arterioscler Thromb 13(2): 296-301. Abstract: The effects of growth hormone treatment of adults with adult-onset pituitary insufficiency on lipoproteins and apolipoproteins were investigated. Nine patients, one women and eight men (age range, 34-58 years), who had been treated for pituitary tumors were studied. They had complete pituitary insufficiency with a duration of at least 1 year. All patients received replacement therapy with thyroid hormones, glucocorticoids, and gonadal steroids. The study had a double-blind, placebo-controlled, crossover design for active treatment with recombinant human growth hormone (0.25-0.5 units/kg per week s.c. given each evening) for 6 months. Fasting serum levels of cholesterol; triglycerides; high density lipoprotein and low density lipoprotein cholesterol; apolipoproteins A-I, B, and E; and lipoprotein (a) were measured before and after 6 and 26 weeks of treatment. Lipoprotein (a) concentrations increased markedly during treatment and were about twice as high compared with pretreatment levels. Serum cholesterol and low density lipoprotein cholesterol concentrations were decreased after 6 weeks of treatment, but levels had returned to pretreatment levels after 26 weeks. High density lipoprotein cholesterol concentrations increased during treatment and were significantly higher than pretreatment levels after 26 weeks of treatment. Serum triglyceride concentrations did not change significantly, but in two patients with marked hypertriglyceridemia, growth hormone treatment resulted in a marked decrease. Serum concentrations of apolipoproteins A-I, B, and E did not change significantly, but changes in apolipoprotein A-I and B concentrations were in parallel to those observed for high density lipoprotein cholesterol and low density lipoprotein cholesterol, respectively.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Growth in utero and serum cholesterol concentrations in adult life Barker, D. J., C. N. Martyn, et al. (1993), Bmj 307(6918): 1524-7. Abstract: OBJECTIVE--To see whether reduced rates of fetal growth are related to raised serum cholesterol concentrations in adult life. DESIGN--Follow up study of men and women whose size at birth had been recorded. SETTING--Jessop and Northern General Hospitals, Sheffield. SUBJECTS--219 men and women born in the Jessop Hospital during 1939-40. MAIN OUTCOME MEASURES--Serum concentrations of total cholesterol, low density lipoprotein cholesterol, and apolipoprotein B. RESULTS--Men and women who had had a small abdominal circumference at birth had raised serum concentrations of total and low density lipoprotein cholesterol and apolipoprotein B. This was independent of the duration of gestation. Serum concentrations of total cholesterol fell by 0.25 mmol/l (95% confidence interval 0.09 to 0.42) with each 1 in (2.54 cm) increase in abdominal circumference. The corresponding figure for serum low density lipoprotein cholesterol was 0.26 mmol/l (0.11 to 0.42) and for serum apolipoprotein B 0.04 g/l (0.02 to 0.07). Small head and chest circumferences at birth and short length were each associated with raised serum low density lipoprotein cholesterol concentrations but the trends disappeared in a simultaneous regression with abdominal circumference at birth. The association between abdominal circumference at birth and low density lipoprotein cholesterol concentration was independent of social class, current body weight, cigarette smoking, and alcohol consumption. CONCLUSION--Raised serum cholesterol concentrations in adult life are associated with impaired growth during late gestation, when fetal undernutrition has a disproportionate effect on liver growth. Impaired liver growth may permanently alter low density lipoprotein cholesterol metabolism. |
| Growth performance, intestinal microbial populations, and serum cholesterol of broilers fed diets containing Lactobacillus cultures Jin, L. Z., Y. W. Ho, et al. (1998), Poult Sci 77(9): 1259-65. Abstract: A study was conducted to determine the effects of adherent Lactobacillus culture on growth performance, intestinal microbial population, and serum cholesterol level of broilers. Four dietary treatments, consisting of the basal diet (control), basal diet + 0.05, 0.10, or 0.15% Lactobacillus culture (LC), were fed to 2,000 Arbor Acres broiler chicks from 1 to 42 d of age (DOA). The chicks were randomly assigned to 40 cages (50 chicks per cage, 10 cages per diet). The experimental period was 42 d. Body weights and feed to gain ratio were measured at 21 and 42 DOA. The intestinal microbial populations and serum cholesterol levels were determined at 10, 20, 30, and 40 DOA. The results showed that body weights and feed to gain ratios were improved significantly (P < 0.05) when compared to control broilers for broilers fed diets containing 0.05 or 0.10% LC, but not 0.15% LC, at 21 and 42 DOA. Coliform counts in the cecum of birds receiving 0.05% LC at 10, 20, and 30 DOA, and 0.10% at 10 and 20 DOA were significantly lower (P < 0.05) than those of the control birds. The total aerobes, total anaerobes, lactobacilli, and streptococci in the small intestines and ceca of the control birds were not significantly different from those of the treated groups. Serum cholesterol levels were significantly lower (P < 0.05) in broilers fed the three diets containing LC at 30 DOA, and in the birds fed 0.05 or 0.10% LC at 20 DOA. |
| Growth until 3 years of age in a prospective, randomized trial of a diet with reduced saturated fat and cholesterol Niinikoski, H., H. Lapinleimu, et al. (1997), Pediatrics 99(5): 687-94. Abstract: OBJECTIVE: Modification of fat intake in childhood may decrease children's future risk for atherosclerosis. Excessive changes in fat intake have been linked with possible growth failure. This study evaluates the effects of a low-saturated fat diet on growth during the first 3 years of life. DESIGN: Half of 1062 healthy infants were randomized at 7 months of age to the intervention group (n = 540) to receive at 1- to 6-month intervals individualized dietary counseling aimed at reducing their exposure to atherosclerosis risk factors. Five hundred twenty-two children served as control children. Growth and serum lipids were measured regularly, and nutrient intakes were analyzed using 3- to 4-day food records at 5- to 12-month intervals. RESULTS: The intervention children consistently consumed slightly less energy than did the control children. The mean fat intake of children in both groups was lower than expected, especially during the first 2 years of life (29.0 SD, 4.7 percentage of energy intake E% and 28.8 4.1 E% in the intervention and control children, respectively, at 8 months, formula-fed children only). At 13, 24, and 36 months, fat intake in the intervention and control children accounted for 26.2 (6.0) and 27.9 (4.9) E%, 29.9 (5.0) and 32.8 (4.8) E%, and 30.8 (4.9) and 33.2 (4.6) E%, respectively. From 13 to 36 months, the baseline adjusted mean serum cholesterol concentration was lower in the intervention children than the control children (95% confidence interval for the difference between means, -0.27 to -0.12 mmol/L). The true mean of the height of the boys in the intervention group during the trial was at most 0.34 cm more or 0.57 cm less (95% confidence interval), and the weight was at most 0.19 kg more or 0.22 kg less than that of the control boys. The respective values for girls were at most 0.77 cm more or 0.16 cm less and at most 0.42 kg more or 0.04 kg less. The numbers of slim children were similar in both groups. CONCLUSIONS: Fat intake by young children is markedly lower than assumed. A supervised low-saturated fat, low-cholesterol diet has no influence on growth during the first 3 years of life. |
| Growth-related modulation of human skin fibroblast cholesterol distribution and metabolism Mazzone, T. and L. Pustelnikas (1990), Biochim Biophys Acta 1047(2): 180-6. Abstract: The relationship between cell growth state and the metabolism and distribution of cellular cholesterol was studied in human skin fibroblasts. Cells made quiescent by serum starvation maintained a smaller fraction of total free cholesterol in a pool susceptible to oxidation by added cholesterol oxidase compared to growing cells. The growth-related differences in the distribution of free cholesterol were magnified in cells which were preincubated in low-density lipoprotein. These latter cells hydrolyzed cholesteryl ester which had accumulated in the presence of LDL, resulting in an increased level of cellular free cholesterol after growth activation. By preincubating cells in 3Hcholesterol linoleate-labeled LDL, it could be demonstrated that activation of cell growth facilitated the appearance of LDL-derived cholesterol in a pool accessible to cholesterol oxidase. These studies suggest that onset of growth in fibroblasts leads to a redistribution of free cholesterol from intracellular to plasma membrane compartments. Furthermore, activation of cell growth in cholesterol loaded cells leads to the net conversion of cholesteryl ester to free cholesterol and most of the latter is in the plasma membrane. |
| Guanidinium-cholesterol cationic lipids: efficient vectors for the transfection of eukaryotic cells Vigneron, J. P., N. Oudrhiri, et al. (1996), Proc Natl Acad Sci U S A 93(18): 9682-6. Abstract: Two cationic lipids, bis-guanidinium-spermidine-cholesterol (BGSC) and bis-guanidinium-trencholesterol (BGTC)-cholesterol derivatives bearing two guanidinium groups-have been synthesized and tested as artificial vectors for gene transfer. They combine the membrane compatible features of the cholesterol subunit and the favorable structural and high pKa features of the guanidinium functions for binding DNA via its phosphate groups. Reagent BGTC is very efficient for transfection into a variety of mammalian cell lines when used as a micellar solution. In addition, both BGTC and BGSC present also a high transfection activity when formulated as liposomes with the neutral phospholipid dioleoylphosphatidyl ethanolamine. These results reveal the usefulness of cholesterol derivatives bearing guanidinium groups for gene transfer. |
| Guar gum and plasma cholesterol. Effect of guar gum and an oat fiber source on plasma lipoproteins and cholesterol in hypercholesterolemic adults Spiller, G. A., J. W. Farquhar, et al. (1991), Arterioscler Thromb 11(5): 1204-8. Abstract: The hypolipidemic effect of guar gum (GG, 15 g/day) was compared with that of an oat fiber source (OFS, 77 g/day). Both treatments supplied the same amount of total dietary fiber (11 g/day) and were taken with water three times a day for 3 weeks at mealtime. Thirteen free-living adult men and women participated in the study. Their total plasma cholesterol (TC) was 244 +/- 21 mg/dl (mean +/- SD), and plasma triglycerides (TGLYs) were 149 +/- 93 mg/dl before the intervention. Diets were monitored to ensure that no changes occurred other than the replacement of carbohydrate calories for the 200 kcal/day supplied by the OFS. Combined averages for both of the crossover phases showed that GG induced a reduction in TC of 26 +/- 10 mg/dl and in low density lipoprotein cholesterol of 25 +/- 9 mg/dl. The OFS induced a reduction in TC of 9 +/- 13 mg/dl and in low density lipoprotein cholesterol of 11 +/- 4 mg/dl. Although both treatments were effective in reducing elevated TC, GG at the levels fed was significantly more effective (p less than 0.001) in reducing TC. Neither treatment induced significant changes in high density lipoprotein cholesterol or very low density lipoprotein cholesterol. |
| Guar gum effects on plasma low-density lipoprotein and hepatic cholesterol metabolism in guinea pigs fed low- and high-cholesterol diets: a dose-response study Fernandez, M. L., D. M. Sun, et al. (1995), Am J Clin Nutr 61(1): 127-34. Abstract: Guinea pigs were fed semipurified diets containing either 0% or 12.5% guar gum (GG) with 0.04% cholesterol or increasing concentrations of GG (0%, 2.5%, 5%, 7.5%, 10%, and 12.5%) with 0.25% cholesterol (by wt). Compared to the 0% GG diet with 0.04% cholesterol, intake of the 12.5% GG diet with 0.04% cholesterol lowered plasma low-density-lipoprotein (LDL) concentrations, the ratio of LDL cholesteryl ester to protein, hepatic cholesterol concentrations, and the activity of acyl-CoA:cholesterol acyltransferase (ACAT), and increased 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and hepatic apo B/E receptor number (P < 0.01). Intake of GG by animals fed 0.25% cholesterol diets resulted in modest effects on hepatic cholesterol pools and plasma LDL concentrations; however, significant negative correlations were found between both plasma LDL cholesterol and hepatic free cholesterol concentrations with the amount of dietary GG (P < 0.05). Hepatic HMG-CoA reductase was suppressed by the 0.25% cholesterol intake, and GG did not reverse this suppression. In contrast, ACAT activity was negatively correlated with the amount of dietary GG (P < 0.05), and GG intake increased the number of hepatic apo B/E receptors at all intakes with the 0.25% cholesterol diets. These results demonstrate that intake of GG significantly alters endogenous cholesterol metabolism by decreasing hepatic cholesterol pools, altering hepatic cholesterol homeostasis, and reducing plasma LDL concentrations. |
| Guar gum reduces serum cholesterol in sea quail fed a cholesterol diet Day, C. E. (1991), Artery 18(3): 107-114. Abstract: Guar gum at 6% and 12% in the diet reduces total serum cholesterol by 31% and 51%, respectively, in male SEA quail fed a diet containing 0.5% cholesterol for a period of one week. Although the potency of hypocholesterolemic action of guar gum in cholesterol fed SEA quail is much less than that in cholesterol fed chickens, SEA quail are a reasonable alternative to chickens for evaluation of guar and similar products, based on other considerations such as smaller size and compound requirements and shorter duration of testing. |
| GUGULIPID: a natural cholesterol-lowering agent Urizar, N. L. and D. D. Moore (2003), Annu Rev Nutr 23: 303-13. Abstract: The resin of the Commiphora mukul tree has been used in Ayurvedic medicine for more than 2000 years to treat a variety of ailments. Studies in both animal models and humans have shown that this resin, termed gum guggul, can decrease elevated lipid levels. The stereoisomers E- and Z-guggulsterone have been identified as the active agents in this resin. Recent studies have shown that these compounds are antagonist ligands for the bile acid receptor farnesoid X receptor (FXR), which is an important regulator of cholesterol homeostasis. It is likely that this effect accounts for the hypolipidemic activity of these phytosteroids. |
| Guidelines for cholesterol management: recommendations of the National Cholesterol Education Program's Adult Treatment Panel II Grundy, S. M. (1994), Heart Dis Stroke 3(3): 123-7. |
| Guidelines for evaluation and treatment of children with elevated cholesterol Williams, C. L. and A. Spark (1991), Ann N Y Acad Sci 623: 239-52. |
| Guidelines from the British Hypertension Society: cholesterol values seem to diverge Burns, G. E. (2004), Bmj 329(7465): 569; author reply 570-1. |
| Guilty until proven innocent: the case of NPC1 and cholesterol Ioannou, Y. A. (2005), Trends Biochem Sci 30(9): 498-505. Abstract: Cholesterol accumulation in the endosomes and lysosomes of Niemann-Pick C (NPC) cells is considered to be the hallmark of this disorder, so the main focus of NPC research has revolved around cholesterol and its role in disease pathogenesis. However, recent data indicate that cholesterol is not the primary culprit in this human lipidosis. I propose a new hypothesis for the potential action or function of the NPC1 protein in the endosome. In this context, the relationship of NPC2 and NPC1 is also discussed. |