| For medical practitioners and the general public - Cholesterol Journal Article Catalog. |
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| Decrease in high density lipoprotein cholesterol during prolonged storage. CELL Study Group Ekbom, T., L. H. Lindholm, et al. (1996), Scand J Clin Lab Invest 56(2): 97-101. Abstract: Different studies on the stability of high density lipoprotein cholesterol (HDL) in frozen serum or plasma have yielded conflicting results, namely increase, decrease, or no change at all during prolonged storage under freezing conditions. As part of a major trial on lipid-lowering strategies we statistically demonstrated a time-related decrease in HDL cholesterol during storage up to 46 months at -20 degrees C. We therefore re-analysed 85 frozen samples that had been analysed fresh and then stored from 26 to 46 months, using the dextran sulphate 500/Mg2+ method. A linear regression analysis of change in HDL cholesterol on time was performed. The slope was significantly negative (p < 0.0005). The regression equation was (decrease in HDL) = 0.05 - 0.008 x (time in months), i.e. after 6 months' storage at -20 degrees C there was almost a 1% decrease in the HDL cholesterol concentration per month of storage. |
| Decrease in plasma cholesterol and regression of atherosclerosis Wang, Y., T. Li, et al. (1995), Zhonghua Nei Ke Za Zhi 34(8): 561-4. |
| Decrease in plasma low-density lipoprotein cholesterol, apolipoprotein B, cholesteryl ester transfer protein, and oxidized low-density lipoprotein by plant stanol ester-containing spread: a randomized, placebo-controlled trial Homma, Y., I. Ikeda, et al. (2003), Nutrition 19(4): 369-74. Abstract: OBJECTIVE: The ester of plant stanols significantly reduces plasma levels of total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) in Western people. Effects of plant stanol ester-containing spread on plasma levels of TC, LDL-C, and apolipoprotein B (apoB) were studied in a randomized, placebo-controlled trial in Japanese subjects whose diet is low in fat and cholesterol. The effects of plant stanol ester on plasma levels of arteriosclerosis-promoting factors, namely remnants of triacylglycerol (TG)-rich lipoproteins, cholesteryl ester transfer protein (CETP), and oxidized LDL (Ox-LDL), were also studied. The assessment of safety was also made. METHODS: One hundred and five healthy volunteers were assigned randomly to one of three groups: placebo spread (n = 35), 2 g/d of plant stanol (3.4 g of stanol ester; n = 34), and 3 g/d of plant stanol (5.1 g of stanol ester; n = 36). Plasma levels of lipids were measured at start of the study, at 2 and 4 wk (end of trial), and at 8 wk (+4 wk). Plasma apoproteins, cholesterol in remnant-like particles which are equivalent to remnants of TG-rich lipoproteins (RLP-C), CETP mass, and Ox-LDL were measured at the beginning and the end of the trial. Plasma levels of plant steroids and fat-soluble vitamins were also measured for the assessment of safety. RESULTS: Background and dietary composition did not differ among groups. Plasma levels of TC, LDL-C, apoB, apoE, CETP mass, and Ox-LDL were reduced significantly by 6.5%, 9.6%, 8.3%, 4.5%, 6.1%, and 20%, respectively, in the 2 g/d plant stanol group. Plasma levels of TC, LDL-C, apoB, CETP mass, and Ox-LDL were decreased significantly by 5.5%, 7.3%, 5.6%, 3.3%, and 19%, respectively, in the 3 g/d plant stanol group. Plasma levels of plant stanols, plant sterols, retinol, beta-carotene, and alpha-tocopherol did not change in any group, but levels of campestanol increased and alpha-tocopherol decreased slightly in the sitostanol groups. CONCLUSION: Plasma levels of TC and LDL-C were significantly reduced by the plant stanol ester-containing spread. The smaller reduction than in Western studies and the lack of dose dependency in this study might be due to the different basal diets. We concluded that plant stanol ester-containing spread is efficacious in reducing plasma LDL-C, apoB, CETP, and Ox-LDL and that 2 g/d plant stanol is adequate for Japanese people. No significant side effects were observed in any group. |
| Decrease in serum LDL cholesterol with microcrystalline chitosan Wuolijoki, E., T. Hirvela, et al. (1999), Methods Find Exp Clin Pharmacol 21(5): 357-61. Abstract: Peroral microcrystalline chitosan (MCCh; 3 capsules, each 400 mg b.i.d.) or placebo was given for 8 weeks in a double-blind manner to 51 healthy obese women just before routine hospital and home meals. Weight records, serum lipids (total, LDL and HDL cholesterol, triglycerides) and safety laboratory parameters were monitored before the trial and at 4, 6 and 8 weeks of treatment. In a subgroup of subjects with a body mass index > or = 30 who had not changed their eating habits, serum LDL cholesterol decreased 0.57 +/- 0.72 mmol/l (n = ll) at 4 weeks in the MCCh group and 0.10 +/- 0.60 mmol/l (n = 14) in the placebo group (p < 0.05). At 8 weeks, LDL cholesterol reduction was 0.48 +/- 0.91 mmol/l in the MCCh group and 0.26 +/- 0.57 mmol/l in the placebo group (p > 0.1). In all subjects, the reduction in LDL cholesterol at 4 weeks was 0.48 +/- 0.72 mmol/l (n = 24) in MCCh subjects and 0.18 +/- 0.58 mmol/l (n = 27) in placebo subjects (p = 0.057), and 0.52 +/- 0.69 mmol/l and 0.31 +/- 0.63 mmol/l, respectively, at 8 weeks (p > 0.1). MCCh did not significantly alter serum total and HDL cholesterol (p > 0.1), but slightly increased serum triglycerides compared to placebo (p = 0.015-0.06). No reductions in weight were observed in any treatment group. Chitosan was well tolerated and no serious adverse events or changes in safety laboratory parameters were noted including serum fat-soluble vitamins A and E, and serum Fe++ and transferrin. |
| Decrease in the level of free cholesterol fraction HDL as a risk factor for threatened atherosclerosis in idiopathic hyperinsulinemia Goldsztajn, P., J. Hartwich, et al. (1993), Kardiol Pol 39(12): 462-9; discussion 470-1. Abstract: Inversive association between concentration of plasma high density lipoprotein (HDL) components and endogenous insulin response to oral glucose uptake was observed in 89 healthy, normolipidaemic, non obese, non diabetic male subjects. Inversive correlation between sum of insulin released during oral glucose tolerance test and HDL free and esterified cholesterol as well as apolipoprotein A1 concentration were confirmed. Coexistence of increased insulin secretion and low ratio of free cholesterol concentration to esterified cholesterol and to proteins in HDL was also observed. In separate group of subjects with normal glucose tolerance in high insulin response subgroup the cholesterol (free and esterified) and protein concentrations were lower than in subgroup with low insulin response. The free cholesterol/esterified cholesterol and free cholesterol/protein (apoA1) ratios were decreased in high insulin response subgroup. It is concluded that low concentration of free cholesterol is a most significant change of HDL composition in hyperinsulinemic, healthy men. |
| Decrease of blood cholesterol and stimulation of antioxidative response in cardiopathy patients treated with endovenous ozone therapy Hernandez, F., S. Menendez, et al. (1995), Free Radic Biol Med 19(1): 115-9. Abstract: Patients with cardiac infarction show a decrease in glutathione peroxidase and superoxide dismutase activities, which are beginners in the scavenger processes of lipid peroxide and superoxide radicals, respectively. In this study, we investigate the effects of endovenous ozone therapy on serum lipid pattern and on antioxidant defense system, such as te glutathione redox one, in the blood of patients with myocardial infarct. Twenty-two patients who had an infarction, between 3 months and 1 year before the study, were treated with ozone by autohemotherapy during 15 sessions. A statistically significant decrease in plasma total cholesterol and low density lipoprotein was observed. High biologically significant increases on erythrocyte glutathione peroxidase and glucose 6-phosphate dehydrogenase activities were found. There was no change in plasma lipid peroxidation level. It was concluded that endovenous ozone therapy in patients with myocardial infarction has a beneficial effect on blood lipid metabolism, provoking the activation of antioxidant protection system. |
| Decrease of cholesterol concentration in human erythrocyte ghosts in old age Brosche, T. and D. Platt (1990), Exp Gerontol 25(1): 23-8. Abstract: The lipid composition of the erythrocyte membrane ghosts of 95 relatively healthy elderly subjects was compared between four age groups: 70 to below 75 years (I), 75 to below 80 (II), 80 to below 85 (III) and 85 to below 90 years of age (IV). The molar ratio of phospholipid to cholesterol (PL/CH) in the erythrocyte ghosts increased with advancing age. Whilst PL levels did not change significantly, a decrease of membrane cholesterol was found. Therefore, the red cell membrane cholesterol seems to parallel the well-known pattern of variation of mean plasma total cholesterol and LDL cholesterol concentrations with age: an increase to a maximum in the sixth decade of life, and a decline thereafter. The processes which are responsible for these changes in cholesterol level with age have not been delineated. However, the findings suggest that one might get different results in studies of age-dependent membrane lipid alterations if rough age group divisions are made (below 30 years of age vs. over 70 years) or to subdivide the group of the elderly. |
| Decrease of P-glycoprotein activity in K562/ADR cells by MbetaCD and filipin and lack of effect induced by cholesterol oxidase indicate that this transporter is not located in rafts Reungpatthanaphong, P., C. Marbeuf-Gueye, et al. (2004), J Bioenerg Biomembr 36(6): 533-43. Abstract: The effect of low-density membrane domains on function of the plasma membrane transporter P-glycoproteine (P-gp), involved in multidrug resistance (MDR) phenotype, has been investigated in K562/ADR cells. To this end we reversibly altered the cholesterol content of K562/ADR cells by using methyl-beta-cyclodextrin as a cholesterol chelator and conversely we repleted them through incubation with cholesterol in culture medium. We also used the cholesterol-binding fluorochrome filipin and cholesterol oxidase. Our data show that either cholesterol depletion or complex formation with filipin resulted in a strong decrease of P-gp activity. However, when cells were incubated with cholesterol oxidase that are known to disrupt rafts, no modification of the P-gp activity was observed. In addition, using a free-detergent methodology to separate by ultracentrifugation, "light," "heavy," and "extra heavy" fractions we show that no P-gp is found in the "light" fraction where rafts are usually detected. Altogether, our data strongly suggest that, in this cell line, P-gp is not localized in rafts. |
| Decreased ability of high density lipoproteins to transfer cholesterol esters in non-insulin-dependent diabetes mellitus Ahnadi, C. E., T. Masmoudi, et al. (1993), Eur J Clin Invest 23(8): 459-65. Abstract: Esterified cholesterol transfer (ECT) from high density lipoproteins (HDL) to very low (VLDL) and low density lipoproteins (LDL) may be abnormal in situations at high risk for atherosclerosis. It has been shown to increase in insulin-dependent diabetes and to decrease in non-insulin-dependent diabetes (NIDD). Since the net transfer of esterified cholesterol (EC) results from a bidirectional exchange between HDL and VLDL/LDL, we developed a transfer assay specifically designed to measure the unidirectional transfer of EC from HDL to lipid emulsions according to first-order kinetics. Our results show that in NIDD the rate constant of HDL-dependent ECT is decreased by 30% by comparison with control subjects. Analysis of HDL composition revealed that, in both groups, HDL-dependent ECT was positively correlated with the free cholesterol/phospholipid ratio (r = 0.94; P < 0.001) and negatively correlated with the triglyceride/EC ratio (r = -0.85; P < 0.001). It is concluded that, besides the known defect of acceptor lipoproteins, the abnormality of ECT in NIDD is also caused by a decreased ability of HDL to act as an EC donor, presumably because of a change in composition. In addition, our work shows that the amount of EC lost by HDL during the reaction transfer is counterbalanced by a reciprocal equimolar transfer of triglycerides. |
| Decreased activity of lecithin:cholesterol acyltransferase and hepatic lipase in chronic hypothyroid rats: implications for reverse cholesterol transport Franco, M., G. Castro, et al. (2003), Mol Cell Biochem 246(1-2): 51-6. Abstract: Chronic hypothyroidism is frequently associated with atherosclerosis due to increased cholesterol plasma levels; nevertheless, the contribution of impaired reverse cholesterol transport (RCT) in this process has not been completely elucidated. The aim of this study was to evaluate the effect of thyroidectomy (Htx) upon the main stages of RCT in rats. Plasma lipid alterations induced by thyroidectomy showed a slight, but significant, reduction of total plasma triglycerides, a 300% increase of LDL-cholesterol and a 25% decrease in HDL-cholesterol compared to control rats. We evaluated the first stage of RCT determining 3H-cholesterol efflux in Fu5AH cells. The capacity of HDL obtained from Htx rats to promote cholesterol efflux was similar to that of controls. Lecithin:cholesterol acyltransferase (LCAT) activity, the second stage and the driving force of RCT was 30% lower in Htx animals compared to controls, as determined by reconstituted HDL used as an external substrate. Lipoproteins are remodeled by hepatic lipase; the mean activity of this enzyme in postheparin plasma of Htx animals was reduced by 30% compared to controls, thus suggesting an impaired HDL remodeling by this enzyme in the hypothyroid status. In contrast, lipoprotein lipase activity in the Htx group was unchanged. In summary, this study demonstrates that chronic hypothyroidism in the rat induced an impaired RCT mainly at the cholesterol esterification, and HDL remodeling mediated by hepatic lipase. The latter probably results in an abnormal HDL structure, i.e. phospholipid enrichment, which contributes to decrease HDL-apo AI fractional catabolic rates. |
| Decreased cellular cholesterol efflux is a common cause of familial hypoalphalipoproteinemia: role of the ABCA1 gene mutations Mott, S., L. Yu, et al. (2000), Atherosclerosis 152(2): 457-68. Abstract: BACKGROUND: High density lipoproteins (HDL) are complex lipoprotein particles involved in reverse cholesterol (C) transport and are negatively associated with the risk for coronary artery disease (CAD). We have described a disorder of familial HDL deficiency (FHD) due to abnormal cellular cholesterol efflux. In the present study, we investigated cellular cholesterol efflux on skin fibroblast from 15 probands with moderate to severe hypoalphalipoproteinemia, including one subject with Tangier disease (TD). We performed family studies on eight of these probands (269 individuals) with familial hypoalphalipoproteinemia (defined as a HDL-C <5th%, and with no known cause of HDL deficiency). We have previously shown that four of our FHD patients and patients with TD have mutations at the ABC1 gene, demonstrating that FHD is a heterozygous form of TD. METHODS: On each subject, we carried out detailed biochemical analysis and determined apoA-I-mediated cellular cholesterol efflux using 3H-cholesterol labeled skin fibroblasts from study subjects compared with controls. TD has also been associated with abnormal cellular cholesterol efflux. Cell fusion experiments with polyethylene glycol (PEG) were carried out with fibroblasts from a subject with TD and one with FHD in order to determine whether the Tangier cells can complement the FHD defect. In all subjects with a reduced cellular cholesterol efflux, exons of the ABCA1 gene were sequenced. RESULTS: Familial forms of HDL deficiency, defined as HDL-C levels <5th percentile, are a heterogeneous group of lipoprotein disorders. A reduced cellular cholesterol efflux has been identified in eight subjects from seven kindred (7/14 or 50% of probands tested), being reduced by a mean 59% of controls (range 49-63%). In four of these subjects, a mutation at the ABCA1 gene locus was identified. In three other subjects an efflux defect was idenfified but no critical mutation at the ABCA1 gene locus has been identified. In the remaining subjects, (7/14), no efflux defect was identified. Complementation studies reveal that the FHD defect is not corrected by Tangier cells, confirming that FHD and TD represent a spectrum of the same genetic defect. CONCLUSION: Familial hypoalphalipoproteinemia syndromes are phenotypically heterogeneous; one form is associated with abnormal cellular cholesterol efflux caused by heterozygous mutations at the ABCA1 gene, that defines familial HDL Deficiency while homozygous mutations or compound heterozygocity causes TD. Other forms are primary hypoalphalipoproteinemia of unknown cause, while the remaining cases are associated with hypertriglyceridemia with or without elevated apoB levels. We conclude that a cellular cholesterol defect is a relatively frequent cause of familial HDL deficiency and that a mutation at the ABCA1 gene can be identified in half of these patients. |
| Decreased cholesterol biosynthesis in fibroblasts from patients with Parkinson disease Musanti, R., E. Parati, et al. (1993), Biochem Med Metab Biol 49(2): 133-42. Abstract: The underlying cause of cellular degeneration in the substantia nigra of patients with Parkinson disease has not been clearly established. With the objective of investigating whether metabolic abnormalities would be detected in peripheral non-neuronal cells, we began assessing key metabolic parameters in skin fibroblasts of these patients. The present report focuses on the finding of a remarkably reduced cholesterol biosynthetic capability of fibroblasts from patients with Parkinson disease. 14C-Acetate incorporation into cholesterol of these fibroblasts was 27.8 +/- 9.4% that observed in normal fibroblasts, and the reduced cholesterol synthesis was confirmed by measuring the activity of the rate-limiting enzyme HMGCoA reductase which averaged 6.64 +/- 2.50 nmol/h/mg protein in the patient's fibroblasts compared to 14.70 +/- 0.69 nmol/h/mg protein in the control fibroblasts. Cholesterol esterifying activity, as cholesteryl oleate formed from 14C-oleate, of the fibroblasts from Parkinson patients, was reduced by an average 43%. Two hypotheses are put forward to link these findings with the current experimental evidences for both increased lipid peroxidation and defective mitochondrial respiratory chain complex I activity in a number of cell types from Parkinson patients. Considering that decreased cholesterol biosynthesis has been detected in all the Parkinson cell lines thus far investigated, it is suggested that this may be a hallmark of the disease. |
| Decreased cholesterol biosynthesis in sitosterolemia with xanthomatosis: diminished mononuclear leukocyte 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and enzyme protein associated with increased low-density lipoprotein receptor function Nguyen, L. B., G. Salen, et al. (1990), Metabolism 39(4): 436-43. Abstract: We investigated the mechanism for reduced cholesterol biosynthesis in sitosterolemia with xanthomatosis. The conversion of acetate to cholesterol and total and active hydroxymethylglutaryl (HMG) coenzyme A (CoA) reductase activities, enzyme protein mass, and catalytic efficiency were related to low-density lipoprotein (LDL) receptor function in freshly isolated mononuclear leukocytes collected at 9 AM after a 12-hour fast from two affected sisters and 12 control subjects. Active HMG-CoA reductase activity was determined in mononuclear leukocyte microsomes prepared and assayed in the presence of sodium fluoride, while total HMG-CoA reductase activity was determined in the absence of the phosphatase inhibitor. Enzyme protein was assayed using rabbit polyclonal anti-rat liver microsomal HMG-CoA reductase serum. The rates at which 14Cacetate was transformed to cholesterol by sitosterolemic mononuclear leukocytes were decreased 29% and 41%, respectively, compared with the mean value for mononuclear leukocytes from 12 control subjects. Similarly, total HMG-CoA reductase activities were 71% and 68% lower in sitosterolemic mononuclear leukocyte microsomes and were associated with 62% and 65% less enzyme protein than the mean for the control microsomal preparations. This marked decrease in HMG-CoA reductase protein mass in sitosterolemic microsomes was partially compensated for by an increase in the proportion of active enzyme. Sitosterolemic plasma and mononuclear leukocyte cholesterol concentrations were not significantly different from control values, although total sterol levels were increased about 20% because of abundant plant sterols. In contrast, receptor-mediated LDL degradation by sitosterolemic mononuclear leukocytes was increased 50% over control.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Decreased cholesterol efflux from fibroblasts of a patient without Tangier disease, but with markedly reduced high density lipoprotein cholesterol levels Eberhart, G. P., A. J. Mendez, et al. (1998), J Clin Endocrinol Metab 83(3): 836-46. Abstract: A 51-yr-old woman without clinical evidence of Tangier disease, but with an extremely low high density lipoprotein (HDL) cholesterol level, was studied. No defect in the major structural protein of HDL, apolipoprotein AI (apo AI), was detected. A preponderance of small HDL particles in the patient's plasma suggested defective uptake of cellular cholesterol. Efflux of 3Hcholesterol from patient fibroblasts to normal apo AI was decreased 50%. Cholesterol efflux to HDL was also decreased, but efflux to trypsin-modified HDL was not. The patient's cells partitioned more exogenously provided 3Hcholesterol into free cholesterol and synthesized greater amounts of phosphatidylcholine than did normal or Tangier fibroblasts. Her fibroblasts did not differ from normal fibroblasts in sterol synthesis rate, cellular cholesterol and cholesterol ester content, or incorporation of oleate into cholesterol ester. The data indicate the presence of a defect in apolipoprotein-dependent cellular cholesterol efflux that differs from that seen in Tangier disease. These findings are the first evidence that other low HDL cholesterol syndromes, besides Tangier disease, may also be associated with cholesterol efflux abnormalities. The identification of mutant genes responsible for apolipoprotein-mediated efflux abnormalities should provide valuable insights into cellular mechanisms involved in the reverse cholesterol transport pathway. |
| Decreased cholesterol level shortens life Ravnskov, U. (1993), Ugeskr Laeger 155(45): 3679-80. |
| Decreased constitutive nitric oxide synthase, but increased inducible nitric oxide synthase and endothelin-1 immunoreactivity in aortic endothelial cells of donryu rats on a cholesterol-enriched diet Aliev, G., J. Shi, et al. (2000), Anat Rec 260(1): 16-25. Abstract: The Donryu rat is resistant to a high cholesterol diet in that typical atheromatous lesions do not develop. Using electron microscopic immunocytochemical techniques, the effects of a CCT diet (4% cholesterol with 1% cholic acid and 0.5% thiouracil) on the distributions of neuronal, macrophage, and endothelial specific nitric oxide synthase (NOS I, NOS II, and NOS III) and endothelin-1 (ET-1) immunoreactivity were examined in the thoracic aortic intima. Atheromatous lesions were absent, but immunocytochemistry showed 1. 4+/-0.52% and 4.0+/-0.9% endothelial cells (EC) with positive staining for NOS I and NOS III, respectively, compared with 16.3+/-2. 5% and 88.6+/-2.48% in control Donryu rats. The CCT-supplemented diet induced expression of NOS II immunoreactivity in thoracic aortic intimal cells. EC, subendothelial macrophages, and smooth muscle cells (SMC) also showed high NOS II-positive staining. The percentage of NOS II-immunoreactive EC was 43+/-1.8%. In control groups, no NOS II immunoreactive cells were observed. The percentage of ET-1 immunopositive cells was also significantly increased by 9. 2+/-0.66% and 64.2+/-1.4% in control and CCT-fed groups, respectively. It is concluded that the administration of a high cholesterol diet in Donryu rats produces endothelial dysfunction associated with changes in the balance of the different isoforms of NOS and ET-1. Therefore, the increase in inducible NOS and ET-1 immunoreactivity seen during the cholesterol-enriched diet appears to be a compensatory reaction of aortic wall cells to the high cholesterol supplementation. |
| Decreased densities of intramembranous particles and cytochemically detectable cholesterol in microvilli of starved rat enterocytes Waheed, A. A., Y. Toyama, et al. (1998), Cell Biol Int 22(3): 177-83. Abstract: The densities of intramembranous particles (IMPs) and of sterol complexes induced by treatment of filipin were studied by freeze-fracture replication of intact intestine and/or isolated brush border membranes (BBM) of well-fed and starved rats. The density of IMPs and filipin-sterol complexes (FSCs) decrease considerably during starvation. Biochemical estimations show a decrease in the levels of cholesterol and proteins with respect to phospholipids during starvation which is in agreement with morphological findings. It is suggested that these changes may play a role in regulating membrane fluidity which in turn affects absorption of nutrients through BBM. |
| Decreased erythrocyte cholesterol/phospholipid ratio in untreated patients with essential hypertension Ronquist, G., G. Frithz, et al. (1992), J Intern Med 232(3): 247-51. Abstract: The erythrocyte cholesterol/phospholipid ratio was determined in eight patients with untreated essential hypertension and compared with that of eight age-matched control subjects. The ratio was significantly lower in patients (Wilcoxon's paired rank test; P less than 0.01), and a correlation existed between the ratio and serum cholesterol concentration in patients (r = 0.63) but not in controls (r = 0.02). A reduction in the cholesterol/phospholipid ratio may play a direct role in destabilizing the plasma membrane, which will in turn result in an increase in membrane permeability in essential hypertension. |
| Decreased HDL cholesterol in subclinical hypothyroidism: the effect of L-thyroxine therapy Caron, P., C. Calazel, et al. (1990), Clin Endocrinol (Oxf) 33(4): 519-23. Abstract: Thyroid function and lipid tests were measured in 29 premenopausal women with subclinical hypothyroidism. This group was compared with 41 euthyroid women matched for age and metabolic parameters. In basal condition there was no difference in thyroid hormone levels between the two groups except for TSH concentration (P less than 0.01). Total cholesterol, triglycerides and apolipoprotein (apo A1, A2, B) of women with subclinical hypothyroidism were not different from controls. HDL cholesterol was significantly decreased in subclinical hypothyroidism compared to the controls (P less than 0.01). With thyroxine therapy, normalization of serum TSH was associated with (1) no significant change in total cholesterol and triglycerides, (2) an increase of HDL cholesterol (P less than 0.01) and apoprotein A1 (P less than 0.05) levels. Total cholesterol/HDL cholesterol ratio was increased in subclinical hypothyroidism (P less than 0.01). During L-thyroxine therapy this ratio returned to normal value. Decreased HDL cholesterol concentration might cause coronary heart disease reported in women with subclinical hypothyroidism. |
| Decreased HDL cholesterol levels but normal lipid absorption, growth, and feeding behavior in apolipoprotein A-IV knockout mice Weinstock, P. H., C. L. Bisgaier, et al. (1997), J Lipid Res 38(9): 1782-94. Abstract: To determine the physiological role of apolipoprotein (apo) A-IV, knockout mice were created by gene targeting in embryonic stem cells. In apoA-IV knockout mice, plasma cholesterol and triglyceride levels were reduced 25% and 44%, respectively, compared with controls. These changes were accounted for by decreased high density (HDL) and very low density lipoprotein (VLDL) levels, respectively, and metabolic studies indicated increased HDL-cholesteryl ester (CE) fractional catabolic rate (FCR) and reduced VLDL transport rate (TR), respectively. ApoA-IV knockout mice had greater than 70% reductions in both hepatic and intestinal apoC-III RNA levels and a similar reduction in the plasma apoC-III level. Complementation analysis, via crossbreeding of a mouse apoC-III transgene onto both the normal and apoA-IV knockout backgrounds, clearly demonstrated that the low triglyceride (VLDL) level in the apoA-IV knockout mice was due to alterations in apoC-III and not apoA-IV. ApoA-IV knockout mice had normal growth, feeding behavior, and lipid absorption, except male mice showed increased food intake in the 2 h after an 18-h fast, suggesting that under some circumstances apoA-IV might serve as a satiety factor. In summary, studies in apoA-IV-induced mutant mice have demonstrated a role for apoA-IV in increasing HDL cholesterol by inhibiting HDL cholesteryl ester FCR yet argue against the apolipoprotein as an overall important mediator of lipid absorption/metabolism. |