Plasma branched chain amino acids are lower in short-term profound hypothyroidism and increase in response to thyroid hormone supplementation

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) mmol/L) compared to a euthyroid reference population (n ¼ 5579; 377 mmol/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) mmol/L, p ¼ .001), but plasma alanine concentrations were unaltered (p ¼ .50). Changes in body weight in response to thyroid hormone supplementation were correlated with changes in plasma BCAA (r ¼ 0.721 p ¼ .001, but not with changes in cholesterol or glucose (p > .80). In conclusion, plasma BCAA concentrations are lower during shortterm 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.

The correlation between serum total bile acid and alanine aminotransferase of pregnant women and the disorders of neonatal hyperbilirubinemia-related amino acid metabolism

“…As a key amino acid to maintain positive nitrogen balance [ 19 ], the expression of ARG was elevated in our study, which might be a stress response of the body in disease conditions. Based on the positive correlation between thyroid hormones and TBA concentrations found by Ceren Golbasi et al [ 27 ], we also hypothesized that with the accumulation of TBA, abnormal thyroid hormone may also lead to the disorder of amino acid metabolism because of the thyroid hormone’s function of promoting amino acid catabolism [ 31 , 32 ]. However, due to the lack of data on thyroid hormones, we were unable to test this hypothesis to further elucidate the mechanism.…”