Background: 3,5-diiodo-L-thyronine (T2) is an endogenous derivative of thyroid hormone. Its physiological role is unclear, but it has been suggested to regulate energy expenditure, resting metabolic rate and oxygen consumption. Thyromimetic effects on the myocardial tissue have also been reported. In this study we evaluate T2 cardiac effects using both in vitro and ex-vivo models . Methods: To investigate T2 effect on cellular metabolism, MTT test and glucose consumption assay were performed on cultured rat cardiomyoblast (H9c2) cells. T2 cellular uptake was also evaluated using High Performance Liquid Chromatography- tandem Mass Spectrometry (HPLC-MS/MS). To assess cardiac functional effects, isolated working rat hearts were perfused with T2 (0.1-10μM) using glucose as energy source and hemodynamic parameters were evaluated for 40min. Results: MTT test results showed that T2 (5nM-10µM) induced a significant increase in cell metabolism (p<0.0001). Glucose consumption was also significantly affected (p<0.01) since we observed an increase in the range of 15% (100nM) to 18% (1μM) compared to control group. HPLC-MS/MS results showed that in the incubation medium T2 (100nM or 1μM) T2 concentration remained nearly constant over time while in cell lysate T2 increased, reaching a steady state after about 60min (0.5 nM, with T2 100nM) or 240min (15nM with T2 1μM) with a recovery of about 90%. Notably, T2 did not produce any significant change in cardiac output nor in heart rate. Conclusions: Our findings indicate that T2 is taken up by cardiomyoblasts and it may modulate cardiac energy metabolism, increasing glucose consumption without affecting the contractile performance.
Effects of 3,5-diiodo-L-thyronine on the cardiac tissue
NGUYEN, NHAT MINH;Leonardo Lorenzini;SACRIPANTI, GINEVRA;Sabina Frascarelli;Alessandro Saba;Riccardo Zucchi;Sandra Ghelardoni
2017-01-01
Abstract
Background: 3,5-diiodo-L-thyronine (T2) is an endogenous derivative of thyroid hormone. Its physiological role is unclear, but it has been suggested to regulate energy expenditure, resting metabolic rate and oxygen consumption. Thyromimetic effects on the myocardial tissue have also been reported. In this study we evaluate T2 cardiac effects using both in vitro and ex-vivo models . Methods: To investigate T2 effect on cellular metabolism, MTT test and glucose consumption assay were performed on cultured rat cardiomyoblast (H9c2) cells. T2 cellular uptake was also evaluated using High Performance Liquid Chromatography- tandem Mass Spectrometry (HPLC-MS/MS). To assess cardiac functional effects, isolated working rat hearts were perfused with T2 (0.1-10μM) using glucose as energy source and hemodynamic parameters were evaluated for 40min. Results: MTT test results showed that T2 (5nM-10µM) induced a significant increase in cell metabolism (p<0.0001). Glucose consumption was also significantly affected (p<0.01) since we observed an increase in the range of 15% (100nM) to 18% (1μM) compared to control group. HPLC-MS/MS results showed that in the incubation medium T2 (100nM or 1μM) T2 concentration remained nearly constant over time while in cell lysate T2 increased, reaching a steady state after about 60min (0.5 nM, with T2 100nM) or 240min (15nM with T2 1μM) with a recovery of about 90%. Notably, T2 did not produce any significant change in cardiac output nor in heart rate. Conclusions: Our findings indicate that T2 is taken up by cardiomyoblasts and it may modulate cardiac energy metabolism, increasing glucose consumption without affecting the contractile performance.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
