Dose and time-dependent hypercholesterolemic effects of iodine excess via TRbeta1-mediated down regulation of hepatic LDLr gene expression

Eur J Nutr. 2010 Aug;49(5):257-65. doi: 10.1007/s00394-009-0081-3. Epub 2009 Nov 16.

Abstract

Background: With the global improvement of iodine nutrition, iodine excess is emerging as a new concern.

Aim of study: The aim of this study is to illustrate the physiological effects and potential molecular mechanisms of excessive iodine intake on lipid metabolism.

Methods: Balb/c mice were given drinking water containing different levels of iodine for 1 month and treated with 1.2 microg/mL iodine for different periods of time, respectively. Plasma lipid parameters and serum thyroid hormones were measured. Expressions of hepatic genes were detected by real-time polymerase chain reactions and Western blot.

Results: Dose-dependent hypercholesterolemic effects were detected in mice (TC, r = 0.615; p < 0.01). Drinking 1.2 microg/mL iodine water for 1 month had no significant effect on serum lipid metabolism, while prolonged exposure induced an increase of serum cholesterol. Serum thyroid hormones were not affected by iodine throughout the study. At the molecular level, we detected a dose-dependent attenuation of hepatic low density lipoprotein receptor (LDLr) and thyroid hormone receptor beta1 (TRbeta1) expression in parallel to the change of serum cholesterol. Treatment with 1.2 microg/mL iodine water for 1 month did not affect LDLr and TRbeta1 expression, while 3 or 6 months exposure resulted in a decrease of their expression.

Conclusion: Present findings demonstrated dose- and time-dependent hypercholesterolemic effects of iodine excess. Furthermore, our data suggests that TRbeta1-mediated down regulation of hepatic LDLr gene may play a critical role in iodine excess-induced hypercholesterolemic effects.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dose-Response Relationship, Drug
  • Down-Regulation / drug effects
  • Drinking
  • Eating
  • Female
  • Hypercholesterolemia / etiology*
  • Hypercholesterolemia / pathology
  • Iodine / administration & dosage*
  • Iodine / urine
  • Lipids / blood
  • Liver / chemistry
  • Liver / metabolism*
  • Liver / pathology
  • Mice
  • Mice, Inbred BALB C
  • Organ Size
  • Polymerase Chain Reaction
  • RNA, Messenger / analysis
  • Receptors, LDL / analysis
  • Receptors, LDL / genetics*
  • Thyroid Gland / pathology
  • Thyroid Hormone Receptors beta / analysis
  • Thyroid Hormone Receptors beta / genetics
  • Thyroid Hormone Receptors beta / physiology*
  • Thyroid Hormones / blood
  • Time Factors
  • Weight Gain

Substances

  • Lipids
  • RNA, Messenger
  • Receptors, LDL
  • Thyroid Hormone Receptors beta
  • Thyroid Hormones
  • Iodine