3-Iodothyronamine (T1AM) is a hormone like molecule structurally similar to TH, that has been reported to modulate energy metabolism by favoring lipid over glucose catabolism. To better understand the role played by T1AM on the regulation of lipid metabolism, in the present study we administered spontaneously obese mice with T1AM at two different dosages (10 and 25 mg/kg per day) for 7 days and the effects on body weight (BW) and lipid profiles were examined. In addition a fluoro-labeled version of T1AM (FL-T1AM) was synthesized and utilized to assess T1AM intracellular localization in 3T3-L1 mouse adipocytes. Administration of 10 or 25 mg/kg per day T1AM showed a BW loss of 10% or 18% of initial BW by day 7 of treatment. T1AM treatment at both dosages produced a significant increase in total plasma triglycerides (P<0.05) and a significant decrease in plasma cholesterol (P<0.05), without any significant change in glycaemia. At present, the specific mechanism of T1AM entry into the cell, as well as its internal targets remains unknown. Cellular imaging revealed rapid intercellular uptake of FL-T1AM without localization to the lipid droplet or nucleus of mature adipocytes. This rapid rate of uptake was further evaluated via flow cytometry, with peak detection of FL-T1AM steadily rising until reaching peak signal and equilibrium at ~20 min. We also observed that when 3T3-L1 adipocytes were treated with T1AM or its synthetic halogen free analog SG-2 (1–10 μM), both compounds decreased lipid accumulation in mature adipocytes, with SG-2 showing a potency significantly higher than T1AM (IC50SG-2=5 μM; IC50T1AM=20 μM). In conclusion T1AM and its synthetic analog show a significant lipolytic activity, both in cultured adipocytes and in vivo.
Lipolytic effects of endogenous 3-iodothyronamine (T1AM) and synthetic analog SG-2 in vivo and in cultured adipocytes
Riccardo ZucchiMembro del Collaboration Group
;Grazia Chiellini
2017-01-01
Abstract
3-Iodothyronamine (T1AM) is a hormone like molecule structurally similar to TH, that has been reported to modulate energy metabolism by favoring lipid over glucose catabolism. To better understand the role played by T1AM on the regulation of lipid metabolism, in the present study we administered spontaneously obese mice with T1AM at two different dosages (10 and 25 mg/kg per day) for 7 days and the effects on body weight (BW) and lipid profiles were examined. In addition a fluoro-labeled version of T1AM (FL-T1AM) was synthesized and utilized to assess T1AM intracellular localization in 3T3-L1 mouse adipocytes. Administration of 10 or 25 mg/kg per day T1AM showed a BW loss of 10% or 18% of initial BW by day 7 of treatment. T1AM treatment at both dosages produced a significant increase in total plasma triglycerides (P<0.05) and a significant decrease in plasma cholesterol (P<0.05), without any significant change in glycaemia. At present, the specific mechanism of T1AM entry into the cell, as well as its internal targets remains unknown. Cellular imaging revealed rapid intercellular uptake of FL-T1AM without localization to the lipid droplet or nucleus of mature adipocytes. This rapid rate of uptake was further evaluated via flow cytometry, with peak detection of FL-T1AM steadily rising until reaching peak signal and equilibrium at ~20 min. We also observed that when 3T3-L1 adipocytes were treated with T1AM or its synthetic halogen free analog SG-2 (1–10 μM), both compounds decreased lipid accumulation in mature adipocytes, with SG-2 showing a potency significantly higher than T1AM (IC50SG-2=5 μM; IC50T1AM=20 μM). In conclusion T1AM and its synthetic analog show a significant lipolytic activity, both in cultured adipocytes and in vivo.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
