HDL clearance and receptor-mediated catabolism of LDL are reduced in hypothyroid rats

Gross, Georg G.; Sykes, Mark; Arellano, Ramiro; Fong, Bessie S.; Ángel, A.

doi:10.1016/0021-9150(87)90070-0

Cited by 31 publications

(8 citation statements)

References 21 publications

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“…Lipoprotein changes in the plasma of rats with experimental hypothyroidism include changes in the VLDL, LDL and HDL fractions. In hypothyroid rats receptor-mediated clearance of LDL is decreased [32][33][34]. Our findings now show that clearance of remnants is also impaired in hypothyroid rats.…”

Section: Discussionsupporting

confidence: 56%

Effects of hypothyroidism on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats

Redgrave

Elsegood

Mamo

et al. 1991

Biochemical Journal

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Methimazole-treated hypothyroid rats were injected intravenously with triacylglycerol/cholesteryl oleate/cholesterol/phospholipid emulsions designed to model the composition of chylomicrons. Compared with controls, hypothyroidism decreased the clearance rates of emulsion cholesteryl oleate. Clearance of emulsion triolein was affected much less and could be accounted for by residual triolein in remnants, suggesting that triacylglycerol lipolysis by lipoprotein lipase was unaffected by hypothyroidism but that clearance of remnants from plasma was decreased. Assays in vitro showed increased activities of lipoprotein lipase and hepatic lipase in hypothyroid rats. Emulsions were incubated with post-heparin plasma lipoprotein lipase to prepare remnants in vitro. The clearance from plasma of pre-formed remnants was slower after injection into hypothyroid rats than in control rats. Uptake of remnant cholesteryl oleate by the liver was significantly decreased in the hypothyroid rats. Treatment of hypothyroid rats for 7 days with 3,3',5'-tri-iodo-L-thyronine (T3) reversed the inhibition of hepatic remnant uptake and normalized plasma cholesterol. A thyroid hormone analogue with decreased hypermetabolic side-effects, L-94901, attenuated plasma cholesterol and improved but did not normalize remnant clearance. Emulsions incubated with plasma from hypothyroid rats had a decreased ratio of apolipoprotein E/apolipoprotein C compared with control rats or hypothyroid rats treated with T3. The change in the apolipoprotein E/apolipoprotein C ratio probably accounts for the defect in remnant clearance in hypothyroidism.

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Section: Discussionsupporting

confidence: 56%

Effects of hypothyroidism on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats

Redgrave

Elsegood

Mamo

et al. 1991

Biochemical Journal

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“…Some [22,40] but not all studies [11,18] sug-gest that catabolism occurs by way of the LDL receptor. The hypercholesterolemia of untreated hypothyroidism is probably due to impaired LDL cholesterol catabolism secondary to a reduced number of LDL receptors [8,19]. In an earlier study [23] we found that thyroxine (T 4) decreased concentrations of apoB and LDL cholesterol but not Lp(a) in hypothyroid patients, supporting the idea that the catabolic pathways of Lp(al and LDL are not identical.…”

Section: Introductionmentioning

confidence: 69%

Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism

Klausen¹,

Hansen²,

Nielsen

et al. 1995

J Mol Med

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Lipoprotein(a) [Lp(a)] is a low-density lipoprotein (LDL) particle in which apolipoprotein B-100 (apoB) is attached to a glycoprotein called apolipoprotein(a) [apo(a)]. Apo(a) has several genetically determined phenotypes differing in molecular weight, to which Lp(a) concentrations in plasma are inversely correlated. High plasma levels of Lp(a) are associated with atherosclerotic diseases. It is therefore of interest to study whether factors other than the apo(a) gene locus are involved in the regulation of Lp(a) concentrations. We measured plasma concentrations of Lp(a) and other lipoproteins and determined apo(a) phenotypes in 31 patients with hyperthyroidism, before and after the patients had become euthyroid by treatment. The mean concentration of LDL cholesterol rose from 2.67 to 3.88 mmol/l (P < 0.01), apoB rose from 0.79 to 1.03 g/l (P < 0.01), and the median Lp(a) concentration increased from 9.74 to 18.97 mg/dl (P < 0.01) on treatment. Lp(a) concentrations were inversely associated to the size of the apo(a) molecule both before (P < 0.01) and after treatment (P < 0.01). The increase in Lp(a) was significant in patients with high molecular weight apo(a) phenotypes (n = 9; P < 0.01) and in patients with low molecular weight apo(a) phenotypes (n = 16; P < 0.01), but not in those with apo(a) "null types" (n = 6; P = 0.5). The low levels LDL cholesterol and apoB in untreated hyperthyroidism may result from increased LDL receptor activity. The increase in Lp(a) levels were not correlated with the increase in LDL cholesterol or apoB.(ABSTRACT TRUNCATED AT 250 WORDS)

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“…Previous studies on the alterations in lipid metabolism during altered thyroid status have implicated a number of factors including changes in the activity of hepatic lipase [28], LCAT [29], triacylglycerol hydrolysis [16], HDL catabolism [30], hepatic cholesterol biosynthesis [31] and biliary cholesterol secretion [32]. Detailed mechanisms for the effects of thyroid hormones on these processes have not been determined.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, the levels of specific mRNA for apolipoproteins in rat liver extracts were measured by dot hybridization [7]. Total poly(A)-rich RNA was detected using 32P-labelled (dT) 30. mRNA levels were quantified by densitometry of auto-radiographs using an LKB Ultroscan XL laser densitometer.…”

mentioning

confidence: 99%

Triiodothyronine increases rat apolipoprotein A‐I synthesis and alters high‐density lipoprotein composition in vivo

Apostolopoulos

Marshall

Howlett

1990

European Journal of Biochemistry

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The effects of altered serum 3,3',5-triiodothyronine levels on rat lipoprotein metabolism were examined. Daily injections of the hormone (50 pg/lOO g body mass) over a period of six days led to an increase of 6.4-fold in the hepatic mRNA level for apolipoprotein(apo)A-I, and a 21% increase in serum apoA-I levels. 12 h after a single injection of 3,3',5-triiodothyronine the rate of [14C]leucine incorporation into apoA-I increased 2.1 fold. Conversely, in hypothyroid rats there was a decrease in hepatic mRNA levels for apoA-I and a decreased rate of [14C]leucine incorporation into apoA-I. The increase in hepatic apoA-I mRNA levels following 3,3',5-triiodothyronine treatment occurred prior to significant changes in serum triacylglycerol levels. High-density lipoprotein (HDL) particles isolated from the serum of hyperthyroid rats were smaller and enriched in apoA-I compared to apoA-IV and apoE. Similar changes in HDL composition were observed following in vitro incubations of normal rat serum with purified rat apoA-I. The results suggest that during altered thyroid status, changes in serum HDL size and composition occur in association with significant changes in apoA-I gene expression.Interest in serum high-density lipoprotein (HDL) levels arises from their postulated role in reverse cholesterol transport [l] and on the basis of their negative correlation with the incidence of coronary heart disease [2, 31. Within this class of lipoproteins there is, however, considerable diversity in both size and composition [4, 51. Some of the heterogeneity of HDL results from changes in lipid composition mediated by lipidmodifying enzymes and exchange proteins. Other sources of the heterogeneity are the result of different apolipoprotein composition. This heterogeneity has functional significance. Studies on the transfer of cholesterol from cell membranes to serum lipoproteins for example [6], demonstrate a role for small apolipoprotein(apo)A-I-containing HDL particles as the initial cholesterol acceptor.The present work focusses on apoA-I synthesis and its potential role in controlling HDL heterogeneity. The work is based on our previous studies which indicate that hepatic mRNA levels for apoA-I [7] and the rate of apoA-I gene transcription [8] are decreased in hypothyroid rats. The effect of direct injection of 3,3',5-triiodothyronine on apoA-I gene expression has now been examined. The results indicate that increased expression of the apoA-I gene in hyperthyroid rats precedes changes in serum triacylglycerol levels and is associated with significant changes in HDL size and composition.

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HDL clearance and receptor-mediated catabolism of LDL are reduced in hypothyroid rats

Cited by 31 publications

References 21 publications

Effects of hypothyroidism on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats

Effects of hypothyroidism on the metabolism of lipid emulsion models of triacylglycerol-rich lipoproteins in rats

Apolipoprotein(a) phenotypes and lipoprotein(a) concentrations in patients with hyperthyroidism

Triiodothyronine increases rat apolipoprotein A‐I synthesis and alters high‐density lipoprotein composition in vivo

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