Effects of hypothyroidism and high-fat feeding on mRNA concentrations for the low-density-lipoprotein receptor and on acyl-CoA:cholesterol acyltransferase activities in rat liver

Salter, Andrew M.; Hayashi, Ryohei; Al‐Seeni, Madeha N.; Brown, Nicholas F.; Bruce, Jennifer; Sørensen, Ole E.; Atkinson, E A; Middleton, Bruce; Bleackley, R. Chris; Brindley, David N.

doi:10.1042/bj2760825

Cited by 58 publications

(41 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Thyroid hormones increase the expression of LDL receptors in rat liver both at mRNA and at the protein level. 33 Putative thyroid hormone-responsive elements are present in the promoter region of the gene encoding for the LDL receptor. 34 It might thus be that the potent inhibition of extrathyroidal T 3 production induced by amiodarone, which causes a very low T3 content of several tissues, including the livery which results in a low T3 receptor occupancy and thereby decreases transcription of the LDL receptor gene.…”

Section: Discussionmentioning

confidence: 99%

Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level

1998

View full text Add to dashboard Cite

General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible.

show abstract

Section: Discussionmentioning

confidence: 99%

Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level

1998

View full text Add to dashboard Cite

show abstract

“…Thyroid hormones can influence the metabolism of cholesterol at several critical steps in the liver, namely increasing LDLR, which mediates cholesterol uptake from the circulation, HMG-CoAR, which controls cholesterol biosynthesis, and cholesterol 7␣-hydroxylase (CYP7AI), the rate-limiting enzyme in the synthesis of bile acids (51)(52)(53). The increase in LDL ϩ VLDL cholesterol observed in virgin and pregnant hypoT rats may be due to the LDL fraction, because it is well known that hypothyroidism increases cholesterol through an enhancement of this fraction (7,54). The elevated serum cholesterol observed in pregnant rats may be the result of higher levels of LDL, in agreement with the decreased expression of hepatic LDLR, making it a risk factor for developing atherosclerosis later in life, even when hypercholesterolemia is temporary and limited to the third trimester in humans.…”

Section: Liver Metabolismmentioning

confidence: 99%

Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats

Hapon

Varas

Jahn

et al. 2005

Journal of Lipid Research

View full text Add to dashboard Cite

Untreated maternal hypothyroidism (hypoT) has serious consequences in offspring development that may result from the effect on lactation of maternal metabolism dysfunction. We studied the effects of prolonged propylthiouracyl (PTU)-induced hypoT (0.1% PTU in drinking water starting 8 days before mating until day 21 of pregnancy or for 30 days in virgin rats) on liver and mammary lipid metabolism and serum lipid concentrations. In virgins, hypoT reduced hepatic mRNAs associated with triglyceride (TG) and cholesterol synthesis (including fatty acid synthase and 3-hydroxy-3-methylglutaryl coenzyme A reductase), and induced lobuloalveolar mammary development. Thyroid hormones influence all major metabolic pathways. Their most obvious and well-known action is an increase in basal energy expenditure through actions on protein, carbohydrate, and lipid metabolism. With specific regard to liver lipid metabolism, thyroid hormones stimulate fatty acid and cholesterol synthesis (1, 2), increase mobilization of plasma cholesterol and triglycerides (TGs) (3, 4), and stimulate fatty acid and cholesterol degradation (5, 6). Disturbances in thyroid function are commonly associated with alterations in plasma lipid levels. Experimental hypothyroidism (hypoT) induced by propylthiouracyl (PTU) treatment is characterized by the accumulation of plasma LDL cholesterol, and decreased VLDL and plasma TGs (7), generally reflecting reduced binding activity of the hepatic LDL receptor (LDLR), which can be normalized after substitution therapy with thyroid hormone (3,8).Pregnancy is a state of dynamic changes in metabolism and nutrient utilization. The insulin-resistant condition and the increase in plasma estrogen levels occurring during late pregnancy are the main factors responsible for the development of a state of maternal hypertriglyceridemia that has been extensively studied in humans and rats (9)(10)(11). This condition benefits the progeny in two ways. First, it supplies essential fatty acids that are critical to normal fetal development and that circulate primarily esterified and associated with lipoproteins. A linear correlation between maternal and fetal plasma TGs has been described that has an important implication in newborn weight (12, 13). Second, it contributes to milk synthesis in preparation for lactation, providing circulating TG in the form of lipoprotein to the mammary gland (MG) for milk lipid synthesis (9).It has been demonstrated that the induction of hypothyroidism in dairy cows suppresses milk production during the treatment period (14). On the other hand, ad-

show abstract

“…For example, it has been shown that estrogen, thyroid hormone, insulin, and glucagon may stimulate LDL receptor expression and lower plasma LDL cholesterol (2,(15)(16)(17)(18)(19). Of particular interest is the recent demonstration that growth hormone (GH) is important for the maintenance of normal cholesterol homeostasis (20)(21)(22)(23).…”

Section: Introductionmentioning

confidence: 99%

Growth hormone and bile acid synthesis. Key role for the activity of hepatic microsomal cholesterol 7alpha-hydroxylase in the rat.

Rudling

Parini²,

Angelin³

1997

J. Clin. Invest.

View full text Add to dashboard Cite

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 ratelimiting enzymes in cholesterol and bile acid biosynthesis, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG CoA reductase) and cholesterol 7 ␣ -hydroxylase (C7 ␣ OH), were reduced by 71 and 64%, respectively. HMG CoA reductase mRNA levels were reduced by 37%, whereas C7 ␣ OH 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 C7 ␣ OH activity was preserved in Hx rats, the activity of C7 ␣ OH 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 C7 ␣ OH. 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 C7 ␣ OH activity.In conclusion, GH has an essential role to maintain a normal enzymatic activity of C7 ␣ OH, and this, at least in part, explains the effects of GH on hepatic cholesterol metabolism. GH is also of critical importance to normalize the al-

show abstract

Effects of hypothyroidism and high-fat feeding on mRNA concentrations for the low-density-lipoprotein receptor and on acyl-CoA:cholesterol acyltransferase activities in rat liver

Cited by 58 publications

References 35 publications

Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level

Amiodarone decreases gene expression of low-density lipoprotein receptor at both the mRNA and the protein level

Effects of hypothyroidism on mammary and liver lipid metabolism in virgin and late-pregnant rats

Growth hormone and bile acid synthesis. Key role for the activity of hepatic microsomal cholesterol 7alpha-hydroxylase in the rat.

Contact Info

Product

Resources

About