Thyroid Function Influences Serum Apolipoprotein B-48 Levels in Patients with Thyroid Disease

Abstract

Aim: Apolipoprotein B-48 (apoB-48) is a major apolipoprotein of intestine-derived chylomicrons (CM) and CM remnants (CMR).Clinically overt hypothyroidism (OH) has been associated with premature and accelerated coronary atherosclerosis. To clarify the clinical significance of apoB-48 measurement in patients with thyroid disease, we investigated the correlations between the serum apoB-48 level and thyroid hormones. Methods: From outpatients of Osaka University Hospital, patients with OH, subjects with subclinical hypothyroidism (SH) and subjects with normal thyroid function were collected and analyzed by measuring serum TSH, FT4 and FT3 levels. Serum apoB-48 levels were measured by a chemiluminescence enzyme immunoassay and the correlations with thyroid hormone levels or lipid profiles were assessed. These levels were compared among subjects with OH, SH and healthy controls. Results: Serum apoB-48 level was correlated with TSH, total cholesterol (TC) and triglycerides (TG), but negatively with FT4 and FT3 level. LDL-C and HDL-C levels were not correlated with serum apoB-48 levels. Serum apoB-48 in patients with OH (7.4±5.9 μg/mL) was significantly higher than in those with hyperthyroidism (5.1±3.5 μg/mL; p＜0.01) and normal subjects (4.7±3.7 μg/mL; p＜0.01), but decreased after levo-thyroxine replacement. ApoB-48, TG and TSH were significantly higher in SH subjects than normal subjects, suggesting that serum apoB-48 level depends on the thyroid function status, similar to TC, LDL-C and TG. Conclusion: Increased serum apoB-48 concentrations and CMR may contribute to the increased risk of atherosclerosis and premature coronary artery disease in the hypothyroid state.

Update on dyslipidemia in hypothyroidism: the mechanism of dyslipidemia in hypothyroidism

“…TH can also reduce the production of ApoB48 and ApoB100, thus reducing the production of VLDL and chylomicron (CM) ( 43 , 44 ). Moreover, ApoB48 levels are negatively correlated to TH ( 45 ). Overall, the reduction of TH inhibits cholesterol synthesis via HMGCR but promotes the absorption of cholesterol through NPC1L1 and reduces catabolism through β-oxidation.…”

“…It has been found that TSH increased the phosphorylation of perilipin and hormone-sensitive lipase (HSL) to increase lipolysis, and circulating FFA increased significantly after TSH injection in vitro studies ( 53 ). Also, TSH could stimulate the increase of ApoB ( 31 , 45 ). So, we could speculate that TSH is capable as a stand-alone hormone to produce a physiological response on lipid metabolism and have an effect independent of TH.…”

“…TH mainly upregulates the activity of lipoprotein lipase (LPL), which could lead to the lipolysis of TRLs, including CM and VLDL; the decrease of TH leads to the attenuation of these effects, thus promoting the elevation of serum TG in hypothyroidism ( 98 ). Studies have shown that impaired hepatic lipase (HL) activity in hypothyroidism patients may also be related to the accumulation of TRL ( 45 ). The transfer of TG to HDL is impaired in subclinical hypothyroidism patients ( 99 ).…”

New insights into the pathological development of dyslipidemia in patients with hypothyroidism

“…Intriguingly, studies have also shown the impaired activity of hepatic lipidosis (HL) in hypothyroidism patients may be also related to the excessive accumulation of TRL [72]. Another research found that the transferring of TG to HDL was significantly impaired in patients with subclinical hypothyroidism, indicating that although intra-vascular metabolism of triglyceride-rich lipoproteins was normal, patients with subclinical hypothyroidism showed abnormalities in HDL metabolism which could be improved by levothyroxine treatment and achievement of euthyroidism [73].…”

Lipid metabolism

“…Conversely, Mugii et al [12] suggest that both hypothyroidism and subclinical hypothyroidism accelerate the accumulation of chylomicrons and chylomicron remnants. They measured apolipoprotein B-48 (apoB-48) and identified a positive correlation with TSH and a negative correlation with free thyroxine and triiodothyronine.…”