Objectives: T1AM is an endogenous natural compound that has opposing physiological effects to those of thyroid hormone. T1AM is thought to switch metabolism from carbohydrate to lipid. Due to its recent discovery, detailed actions of T1AM on affected metabolic pathways are still unknown. In a previous pilot study, we observed that subchronic low doses of T1AM could significantly increase lipolysis in mice. The present work is focused on studying the effects of T1AM on carbohydrate and lipid metabolism in obese mice using Nuclear Magnetic Resonance (NMR) spectroscopy by dynamic metabolomics. This novel way of monitoring all serum metabolites simultaneously in individual animals in response to T1AM could potentially identify pathways through which T1AM acts. Methods: To distinguish carbohydrate from lipid pathways, we used 13C-glucose labeling in three groups of spontaneously overweight mice: Group1: five obese control mice injected with saline once daily for seven days; Group 2: five obese mice injected with T1AM (10 mg/kg/day) once daily for seven days; Group 3: same as in Group 2 but using an higher dose of T1AM (25 m/kg/day). The mice were monitored prior to and after the week of injections. In particular we examined small molecules intermediates in carbohydrate and lipid metabolism, appetite through food intake, and weight measurements over the course of four weeks. Results: We observed that exogenous T1AM administration was associated with a body weight loss trend. After T1AM withdrawal, mice regained only part of lost weight in the following 2 weeks, indicating long-lasting effects of this natural molecule. No difference in food intake was observed at any time. NMR metabolic profiling experiments are currently underway to better identify key changes in fuel and energy metabolism. Conclusions: T1AM produced beneficial effects in obese mice and might become an effective human weight-loss drug.
Metabolome dynamics of T1AM, an endogenous thyroid hormone derivative: Effects on lipid metabolism, weight loss, and appetite in mice.
GHELARDONI, SANDRA;ZUCCHI, RICCARDO;CHIELLINI, GRAZIA
2012-01-01
Abstract
Objectives: T1AM is an endogenous natural compound that has opposing physiological effects to those of thyroid hormone. T1AM is thought to switch metabolism from carbohydrate to lipid. Due to its recent discovery, detailed actions of T1AM on affected metabolic pathways are still unknown. In a previous pilot study, we observed that subchronic low doses of T1AM could significantly increase lipolysis in mice. The present work is focused on studying the effects of T1AM on carbohydrate and lipid metabolism in obese mice using Nuclear Magnetic Resonance (NMR) spectroscopy by dynamic metabolomics. This novel way of monitoring all serum metabolites simultaneously in individual animals in response to T1AM could potentially identify pathways through which T1AM acts. Methods: To distinguish carbohydrate from lipid pathways, we used 13C-glucose labeling in three groups of spontaneously overweight mice: Group1: five obese control mice injected with saline once daily for seven days; Group 2: five obese mice injected with T1AM (10 mg/kg/day) once daily for seven days; Group 3: same as in Group 2 but using an higher dose of T1AM (25 m/kg/day). The mice were monitored prior to and after the week of injections. In particular we examined small molecules intermediates in carbohydrate and lipid metabolism, appetite through food intake, and weight measurements over the course of four weeks. Results: We observed that exogenous T1AM administration was associated with a body weight loss trend. After T1AM withdrawal, mice regained only part of lost weight in the following 2 weeks, indicating long-lasting effects of this natural molecule. No difference in food intake was observed at any time. NMR metabolic profiling experiments are currently underway to better identify key changes in fuel and energy metabolism. Conclusions: T1AM produced beneficial effects in obese mice and might become an effective human weight-loss drug.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
