Dose and time-dependent hypercholesterolemic effects of iodine excess via TRbeta1-mediated down regulation of hepatic LDLr gene expression.
BACKGROUND
With the global improvement of iodine nutrition, iodine excess is emerging as a new concern.


OBJECTIVE
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.


CONCLUSIONS
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.
Zhao
Li-Na
LN
Department of Nutrition and Food Hygiene, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, 430030, Wuhan, Hubei, China.
Xu
Jian
J
Peng
Xiao-Lin
XL
Tian
Li-Yue
LY
Hao
Li-Ping
LP
Yang
Xue-Feng
XF
Ying
Chen-Jiang
CJ
Sun
Xiu-Fa
XF
D000818:Animals; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004326:Drinking; D004435:Eating; D005260:Female; D006937:Hypercholesterolemia / Q000209:etiology* / Q000473:pathology; D007455:Iodine / Q000008:administration & dosage* / Q000652:urine; D008055:Lipids / Q000097:blood; D008099:Liver / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D009929:Organ Size; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000032:analysis / Q000235:genetics*; D013961:Thyroid Gland / Q000473:pathology; D037042:Thyroid Hormone Receptors beta / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D013963:Thyroid Hormones / Q000097:blood; D013997:Time Factors; D015430:Weight Gain
D008055:Lipids; D012333:RNA, Messenger; D011973:Receptors, LDL; D037042:Thyroid Hormone Receptors beta; D013963:Thyroid Hormones; D007455:Iodine