Serum concentrations of remnant-like particles in hypothyroid patients before and after thyroxine replacement.
ABSTRACT Remnant-like particles (RLPs) reflect chylomicron remnants and very-low-density lipoprotein remnants, which are most likely to be atherogenic particles. To investigate the effect of thyroxine replacement on the metabolism of RLPs in hypothyroidism, we measured serum concentrations of RLPs during an oral fat-loading test in patients with hypothyroidism before and after thyroxine replacement.
Thirteen patients with hypothyroidism, having serum-free thyroxine (FT4) of 4.25 +/- 2.23 pmol/l (mean +/- SD) and TSH of 72.5 +/- 27.7 mU/l, participated in the study. Two-hundred grams of cream containing 32.9% of fat were given to each patient followed by blood draws every 2 h for 8 h. The patients became euthyroid after 3 months of T4 replacement, and the fat-loading tests were then repeated.
Fasting levels of serum total cholesterol and low-density lipoprotein cholesterol were remarkably decreased after T4 therapy (P < 0.0005). Serum high-density lipoprotein cholesterol and triglyceride were also decreased by T4 therapy, not so remarkably but significantly (P < 0.05). Activities of lipoprotein lipase (LPL) and hepatic triglyceride lipase (HTGL) increased 52% and 85%, respectively, from the pretreatment values. Serum concentrations of remnant-like particle cholesterol (RLP-C) and remnant-like particle triglyceride (RLP-TG), measured by immunoseparation assays, significantly decreased from 0.14 +/- 0.03 to 0.09 +/- 0.03 mmol/l (P < 0.0005) and from 0.19 +/- 0.11-0.11 +/- 0.07 mmol/l (P < 0.01), respectively. In the fat-loading test, serum low-density lipoprotein cholesterol concentrations were not changed, while serum RLPs concentrations were increased and remained high throughout the test, with the peak value at 6 h in a hypothyroid condition. In an euthyroid condition after T4 therapy, the peak values of RLPs were obtained at 4 h, and the concentrations were decreased rapidly. As the result, areas under the curve of serum RLPs were decreased remarkably after T4 therapy.
Hypothyroidism seems to be associated with a decrease in metabolism of serum RLPs. Such altered metabolism of RLPs may be related to the decreased activities of LPL and HTGL and can be corrected by T4 replacement therapy.
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ABSTRACT: Thyroid hormones play an important role in regulating energy homeostasis and lipid and glucose metabolism. This study assessed the relationship between free thyroxine and clinical features of metabolic syndrome (MS). A total of 4,938 Taiwanese subjects (2,891 men and 2,047 women with a mean age of 50.1+/-12.6 years) with normal serum free thyroxine levels were enrolled. A modified National Cholesterol Education Program definition of MS was adopted substituting body mass index (BMI) for waist circumference. Serum free thyroxine concentrations were determined by immunoassay. Overall, 14% of subjects had a high fasting glucose, 27% had high blood pressure, 14% had high serum total triglyceride, 8% had low high-density lipoprotein cholesterol, and 18% were obese. The serum free thyroxine concentrations showed a statistically significant correlation with triglyceride and body mass index, respectively (P<.01), but not with blood pressure, glucose level, or high-density lipoprotein cholesterol level. According to the presence of 0, 1, 2, and 3 or more features of MS, age and sex-adjusted means of serum free thyroxine were 17.8+/-3.7, 17.6+/-3.7, 17.5+/-3.7, and 17.1+/-3.3 pmol/L, respectively, with a modest, but statistically significant, decreasing trend (P<.05). When comparing subjects in the highest and lowest quartile of free thyroxine, the former group demonstrated a 2-fold decrease in the odds ratio for MS with 3 or more metabolic features. Low circulating free thyroxine levels, albeit normal, were associated with MS in a Chinese population. Further study is necessary to document the role of thyroid hormones in metabolic abnormalities of MS.Metabolism 12/2005; 54(11):1524-8. · 3.10 Impact Factor
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ABSTRACT: This study was to assess the relation of thyroid dysfunction to metabolic syndrome (MetS) at an earlier stage in Korean population. Metabolic parameters such as body composition, blood pressure (BP), fasting glucose, total cholesterol, triglyceride (TG), HDL-cholesterol (HDL-C), LDL-cholesterol (LDL-C), thyroid-stimulating hormone (TSH) and free thyroxine 4 (fT(4)) were measured. During a mean follow-up of 3 yr, 5,998 Koreans ages over 18 yr were assessed. There were 694 cases of MetS at follow-up. The mean age of the subjects was 45.6 ± 9.5 yr. Mean level of TSH was 2.02 ± 1.50 mIU/L, mean level of fT(4) was 1.23 ± 0.20 ρM/L. At baseline, TSH levels and fT(4) levels were associated to waist circumference, BP, glucose and lipids in the subjects. Increase in systolic blood pressure, diastolic blood pressure (DBP), total cholesterol and TG were significantly associated with changes in TSH levels after adjustment. Changes in DBP, TG, HDL-C and fasting glucose were significantly associated with changes in fT(4) levels after adjustment. Increase in TSH levels even after further controlling for baseline TSH level predicted the MetS over the study period. In conclusion, there is a relationship between thyroid function and cardiovascular risk factors, such as BP, total cholesterol, TG, HDL-C and fasting glucose. Also, higher levels of TSH may predict the MetS in Korean.Journal of Korean medical science 04/2011; 26(4):540-5. · 0.84 Impact Factor
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ABSTRACT: Background: The atherogenic effects of hypothyroidism on lipid metabolism could result, in part, from the reduced clearance of remnant lipoproteins. In this study, we investigated the expression of hepatic low-density lipoprotein receptor-related protein 1 (LRP1), a receptor for remnant lipoproteins, in hypothyroidism and the effect of triiodothyronine (T3) treatment on hepatic LRP1 expression. Methods: C57BL/6 mice were fed a normal diet (control group) or a low iodine diet supplemented with 0.15 % propylthiouracil (PTU/LI group) for 4 weeks. Mice in PTU/LI group were injected intraperitoneally with T3 (0, 30, and 150 μg/kg of body weight) for 7 days. HepG2 cells were incubated in fetal bovine serum (FBS) or charcoal-stripped FBS (CSS) with various concentrations of T3. The expression and function of LRP1 in liver samples and cells were analyzed. Results: Hypothyroidism was successfully induced in PTU/LI group mice. Hepatic LRP1 protein expression was lower in the PTU/LI group than the control group. T3 treatment up-regulated hepatic LRP1 protein expression in PTU/LI group mice. LRP1 expression in HepG2 cells was reduced after incubation in media containing CSS, which mimics hypothyroidism in vitro, and was recovered by T3 treatment. The protein expression of LRP1 in HepG2 cells was increased by T3 treatment in a dose-dependent manner up to 2.0 nM T3. However, LRP1 mRNA transcription was not affected by hypothyroidism conditions or T3 treatment, either in liver samples or HepG2 cells. T3 treatment on HepG2 cells increased cellular uptake of lipid-conjugated apolipoprotein E through LRP1. Conclusions: Our data demonstrate that hepatic LRP1 expression and function decrease in hypothyroidism and are regulated by thyroid hormone. These results suggest that in hypothyroidism, decreased expression of hepatic LRP1 may be associated with reduced clearance of circulating remnant lipoproteins.Thyroid: official journal of the American Thyroid Association 03/2013; · 2.60 Impact Factor