Introduction: 3-Iodothyronamine (T1AM) is a novel thyroid hormone derivative, which has been detected in rat blood and tissues. In vivo, T1AM has been reported to produce several functional effects, including the switch of fuel utilization from carbohydrates to lipids. In the present work we used rat white adipocytes to investigate T1AM uptake, metabolism, and metabolic effects.
Methods: Rat white adipocytes were incubated with exogenous T1AM. The concentrations of T1AM, thyronamine, 3-iodothyroacetic acid and thyroacetic acid were assayed by HPLC coupled to tandem mass spectrometry. Palmitate uptake was measured radiochemically using [3H]-2-D-dideoxyglucose (1 microM; 1 mCi/ml) and [14C]-palmitic acid (100 microM; mCi/ml) respectively. Type A and type B monoamine oxidase activities (MAO-A and MAO-B) and semicarbazide-sensitive amine oxidase activity (SSAO) were studied radiochemically, using [14C]-serotonin or [14C]-benzylamine as substrates, in the absence and in the presence of T1AM.
Results: T1AM was significantly taken up by rat white adipocytes. Intracellular catabolism included oxidation to 3-iodothyroacetic acid and deiodination to thyronamine. T1AM (from 50 nM to 10 microM) did not affect baseline glucose or palmitate uptake. However, T1AM inhibited insulin-stimulated glucose and palmitate uptake with IC50s of 1.4 microM. and 18 nM, respectively. In addition, T1AM inhibited benzylamine oxidation by MAO-B and SSAO with IC50s of 6.5 and 3.3 nM respectively, whereas no inhibition was observed with regard to the oxidation of serotonin, a MAO-A substrate.
Conclusions: T1AM antagonizes the effects of insulin on glucose and palmitate uptake by rat white adipocytes. T1AM is taken up by adipocytes, where it is a high affinity target of plasma membrane SSAO and mitochondrial MAO-B.
30 Apr - 04 May 2011
European Society of Endocrinology