Effect Of Iodine Excess On Lipid Metabolism And Its Underlying Mechanism

Iodine is an essential trace element which is an essential constituent of the thyroid hormones.Thyroid hormones play an important role in the regulation of metabolism and growth. Adequate iodine intake lays solid foundation for maintaining normal thyroid function. Iodine deficiency disorders (IDD) have been prevalent in the world and created serious hazards to public health. The goal of eliminating iodine deficiency disease (IDD) has been achieved since Universal Salt Iodization (USI) policy has been widely carried out in many nations. With rapid global progress in correcting iodine deficiency, reports are increasingly appearing on the higher prevelance of all kinds of thyroid diseases caused by excessive iodine intake in the recent decades. Iodine excess and its health hazards are immerging as a new public health problem.Present studies on the hazard effects of iodine excess were focus on its effect on thyroid function. Wheras studies on the extrathyroidal effects of the iodine excess are rare. However, our group has found the dyslipidemia caused by iodine excess in both rats and mice during the toxicological study of excessive iodine intake. In addition, the dose-dependent hypercholesterol effect of iodine excess has also been reported in laying hens by foreign scholars. Moreover, the first report on the epidemiological correlation between high water iodine and dyslipideima was published in domestic in 2009. Increasing evidences have suggested that iodine excess may have a potential effect on dyslipideima. Prevalence of dyslipidemia in China significantly increased in recent decades due to rapid economic growth, the higher living standards, as well as evident trends in Western dietary pattern. According to The Chinese Nutrition and Health Survey, prevalence of hyperlipidemia in adult was 18.8%, patients with hyperlipidemia were up to 160 million. Hyperlipidemia is the most important risk factor for cardiovascular disease. Every year China spends more than 200 billion yuan on medical expenses and labor costs due to cardiovascular diseases and it is also a heavy burden both to society and to the family. Therefore, the relationship between Iodine excess and dyslipidemia deserves more attention and further study.Animal experiments and epidemiological study are combined in the present study. To investigate the time and dose effect of iodine excess on lipid metabolism and its underlying mechanism in animal models of iodine excess under different dietary patterns; To investigate the correlation between different iodine nutrition and the prevalence of dyslipidemia and further to determine wether the iodine nutrition is the risk factor for dyslipidemia. At present China is facing the adjustment of the strategy of Universal Salt Iodization, this study will further expand our knowledge on the potential hazards of iodine excess on health and the results will be instructive for reasonable iodine intake.Aim of study:The aim of this study is to illustrate the physiological effects and potential mechanisms of excessive iodine intake on lipid metabolism.Methods:Balb/c mice were given drinking water containing different levels of iodine for one month and treated with 1200μg/L iodine for different period time respectively. Plasma lipid parameters and serum thyroid hormones were measured. Hepatic type 1 deiodinase activity and oxidative stress parameters were evaluated. Expressions of hepatic genes were detected by real time polymerase chain reactions and Western blot.Results:①Dose-dependent hypercholesterolemic effects were detected in mice (TC:r= 0.615, P＜0.01). Drinking 1200μg/L iodine water for 1 month had no significant effect on serum lipid metabolism while prolonged exposure induced an increase of serum cholesterol.②An obvious colloid goiter was observed in thyroid of mice exposed to high doses of iodine.The diameter of the thyroid Follicular gradually increased as the dosage of iodine increased.③Serum thyroid hormones were not affected by iodine throughout the study. Excessive iodine intake decreased the TAOC antioxidant ability and increased the MDA content in serum and liver mice in a dose-dependant manner. MDA level in serum and liver elevated obviously when iodie dosage was up to 2400μg/L. drinking 1200μg/L iodine water for 1 month did not affect oxidative stress parameters while prolonged exposure induced an increase of MDA level in serum and liver. Hepatic D1 activity was not affected by iodine throughout the study.④A dose-dependent attenuation of hepatic Low Density Lipoprotein receptor (LDLR) and Thyroid hormone receptorβ1 (TRβ1) expression were detected in parallel to the change of serum cholesterol. Treatment with 1200μg/L iodine water for 1 month did not affect LDLR and TRβ1 expression, while 3 months or 6 months exposure resulted in a decrease of their expression.Conclusion:Present findings demonstrated a dose and time dependent hypercholesterolemic effects of iodine excess. Furthermore, our data suggests that TRβ1 mediated down regulation of hepatic LDLR gene may play a critical role in iodine excess induced hypercholesterolemic effects. Aim of study:The aim of this study is to illustrate the combined effect of iodine excess and high fat diet on lipid metabolism and its mechanism.Methods:Balb/c mice were given drinking water containing different levels of iodine for one month and treated with 1200μg/L iodine for different period time respectively. Animals were feed with high fat diet which was made in our laboratory.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:①an obvious colloid goiter was observed in thyroid of mice exposed to excessive iodine combined high fat diet.The weight of the thyroid gradually increased as the dosage of iodine increased. Follicular fusion and part of the Follicular rupture occurred in the 2400μg/L and 4800μg/L iodine combined high fat diet groups. The damage in the thyroid were gradually serious with prolonged exposure to 1200μg/L iodine combined high fat diet.②Iodine excess combined high fat diet led to a synergistic effect on oxidative damage in mice. Chronic iodine excess combined high fat diet intake resulted in a decrease of the SOD and GSH-Px activity and an increase of MDA level.③Compared with the high fat diet group, Iodine intake (≤4800μg/L) in drinking water combined high fat diet for 1 month had no effect on serum thyroid hormones (TT4,TT3,TSH) and serum lipids. Exposure to 1200μg/L iodine combined high fat diet for 3,6 month resulted in abnormal thyroid hormone metabolism (TT4,TT3 elevated,TSH dereased) and abnormal serum lipid metabolism (TC, TG, LDL-C decreased).④Compared with the high fat diet group, exposure to iodine excess combined high fat diet for 1 month (iodine dosage≤4800μg/L) did not affect LDLR and SR-BI expression; exposure to 1200μg/L iodine water combined high fat diet for 1 month did not affect LDLR and SR-BI expression, while 3 months or 6 months exposure resulted in an increase of LDLR expression.Conclusion:Present findings demonstrated iodine excess combined high fat diet could cause damage to the thyroid and lead to thyroid hormone disorder. Those in turn resulted in the changes in serum lipids. Up regulation of hepatic LDLR gene might be an important molecular mechanism of the changes in serum lipids induced by iodine excess combined high fat diet.Aim of study:To investigate the association between different iodine nutriton and the prevelance of dyslipidemia in a representative sample of subjects in Shenzhen and to investigate whether the abnormal iodine nutrition is the risk factor for dyslipidemia.Study design:A total of 326 adult from 2 dififerent communities in shenzhen, aged 30 to 85 years were included in the study. Body weight and height were measured, the urine iodine concertration and serum lipid and serum glucose level were measued. A questionnaire was given to the subject about general information and risk factors for dyslipidemia.Results:①the prevalence of dyslipidemia in the sample was 33.72%, males 39.02% and females 31.28%. The prevalence of dyslipidemia was significantly different among different age groups. The highest prevalence of dyslipidemia was 53.13% in 60 to 70 age group.②the median urinary iodine in the sample was 167.7μg/L. there were large individual differences in level of urinary iodine, with the 15.64%; urinary iodine concentration 200-300μg/L accounted for 45.09% in the sample.③when the urine iodine concentration<200μg/L,There is a reverse relationship between iodine nutrition and prevalence of HDL-C(rs=-0.164,p=0.031); when the urine iodine concentration>300μg/L,There is a positive relationship between iodine nutrition and prevalence of HDL-C(rs=0.246,p=0.013); there was no significant correlation between Other lipid parameters and urinary iodine concentration.④Multivariate Logistic regression analysis showed that:Age, high blood glucose, abdominal obesity was significantly related the prevalence of dyslipidemia; urine iodine concentration was no significant correlation the prevalence of dyslipidemia.Conclusion:the prevalence of dyslipdemia in Shenzhen is high, the prevention and treatment of dyslipidemia is in an urgent need. The percent of urinary iodine above 200μg/L is high in local residents and there may be a risk of iodine excess and its hazard effect. There may be a U typed relationship between iodine nutrition and the prevalence of HDL-C abnormality. Further studies are needed to make sure whether iodine nutrition is an influencing factor of dyslipidemia...