Abstract

Branched chain amino acids (BCAA) are implicated in the pathogenesis of cardiometabolic diseases conceivably by affecting insulin resistance and mitochondrial dysfunction. Circulating BCAA levels may predict (subclinical) atherosclerosis, diabetes and hypertension development but the factors involved in BCAA regulation are incompletely understood. Given the key role of thyroid hormones on many metabolic processes including protein metabolism, we aimed to determine effects of thyroid dysfunction on circulating BCAA. Effects of short-term profound hypothyroidism on plasma BCAA were determined in 17 patients who had undergone total thyroidectomy for differentiated thyroid carcinoma. Patients were studied during hypothyroidism, i.e. after thyroidectomy, and after thyroid hormone supplementation. Plasma BCAA (sum of valine, leucine and isoleucine) and alanine were measured by nuclear magnetic resonance spectroscopy. During hypothyroidism (median thyroid-stimulating hormone 81 (IQR 67–120.5) mU/L), plasma BCAA were lower (255 (IQR 222–289) µmol/L) compared to a euthyroid reference population (n = 5579; 377 µmol/L (2.5th to 97.5th percentile 258–548), p < 0.001). After 20 weeks of thyroid hormone supplementation (thyroid-stimulating hormone 0.03 (IQR 0.01–0.14 mU/L) plasma BCAA had increased (328 (IQR 272–392) µmol/L, p = .001), but plasma alanine concentrations were unaltered (p = .50). Changes in body weight in response to thyroid hormone supplementation were correlated with changes in plasma BCAA (r = 0.721 p = .001, but not with changes in cholesterol or glucose (p > .80). In conclusion, plasma BCAA concentrations are lower during short-term profound hypothyroidism in humans, and increase in response to thyroid hormone supplementation. Changes in BCAA and in body weight after reversal of the hypothyroid state appear to be interrelated.

摘要

可以想象，支链氨基酸 (BCAA) 通过影响胰岛素抵抗和线粒体功能障碍而与心脏代谢疾病的发病机制有关。循环支链氨基酸水平可以预测（亚临床）动脉粥样硬化、糖尿病和高血压的发展，但对支链氨基酸调节所涉及的因素尚不完全了解。鉴于甲状腺激素在包括蛋白质代谢在内的许多代谢过程中的关键作用，我们旨在确定甲状腺功能障碍对循环支链氨基酸的影响。在 17 名因分化型甲状腺癌行全甲状腺切除术的患者中确定了短期严重甲状腺功能减退对血浆 BCAA 的影响。在甲状腺功能减退期间，即在甲状腺切除术后和补充甲状腺激素后对患者进行了研究。血浆支链氨基酸（缬氨酸的总和，亮氨酸和异亮氨酸）和丙氨酸通过核磁共振波谱测量。在甲状腺功能减退症（中位促甲状腺激素 81 (IQR 67–120.5) mU/L）期间，与甲状腺功能正常的参考人群相比，血浆 BCAA 较低（255 (IQR 222–289) µmol/L）。n  = 5579；377 µmol/L（第 2.5 至第 97.5 个百分位数 258–548），p  < 0.001）。补充甲状腺激素 20 周后（促甲状腺激素 0.03（IQR 0.01–0.14 mU/L）血浆 BCAA 增加（328（IQR 272–392）μmol/L，p  = .001），但血浆丙氨酸浓度未改变( p  = .50). 补充甲状腺激素引起的体重变化与血浆 BCAA 的变化相关（r  = 0.721 p  = .001，但与胆固醇或葡萄糖的变化无关（p > .80）。总之，在人类短期严重甲状腺功能减退期间，血浆 BCAA 浓度较低，并且在补充甲状腺激素后会增加。甲状腺功能减退状态逆转后 BCAA 和体重的变化似乎相互关联。