3-Iodothyronamine (T1AM), an endogenous fast acting thyroid hormone derivative: novel evidence for weight loss and glucose co-regulation by RNA gene expression

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 414-436-HPT Axis Biology & Action
Basic/Translational
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-422
Fariba Assadi-Porter*1, Grazia Chiellini2, Riccardo Zucchi2, Marco Tonelli3, Hannah Reiland3, Thomas S Scanlan4, Sandra Ghelardoni2, Vittoria Carnicelli5 and Dan Butz3
1University of Wisconsin-Madison, Madison, WI, 2University of Pisa, 3University of Wisconsin Madison, 4Oregon Hlth & Science Univ, Portland, OR, 5university of Pisa
3-Iodothyronamine (T1AM), an endogenous fast acting thyroid hormone derivative: novel evidence for weight loss and glucose co-regulation by RNA gene expression.

 

Fariba M. Assadi-Porter1, Hannah Reiland1, Vittoria Carnicelli2, Dan Butz1, Marco Tonelli1, Sandra Ghelardoni2, Thomas S. Scanlan3, Riccardo Zucchi2, Grazia Chiellini2.

1University of Wisconsin-Madison, Madison, WI (USA), 2University of Pisa, Pisa, Italy; 3Oregon Health and Science University, Portland, OR (USA)

3-iodothyronamine (T1AM) is an endogenous fast-acting thyroid hormone derivative. In rodents, treatment with high single doses of T1AM has produced profound metabolic effects (1). In a recent study we provided the first evidence that subchronic low doses of T1AM increased lipolysis associated with significant weight loss but independent of food consumption(2). In the present work we investigated the effects of a multi doses (10 mg and 25 mg/Kg /day) subchronic T1AM treatment on metabolism at the molecular level. At this aim, we examined small molecule intermediates in carbohydrate and lipid metabolism using Nuclear Magnetic Resonance (NMR) associated to organ specific (liver, adipose tissue, pancreas, muscle and heart) RNA gene expression analysis.

Our preliminary novel finding is that subchronic low doses of T1AM (10 mg/Kg/day and 25 mg/Kg/day) can act as a master regulator of both glucose and fat metabolism in obese mice. Infact, in addition to changes in plasma levels of small molecular size metabolic markers (such as glucose, piruvate, lactate, acetate, ketone bodies and aminoacids) which confirm the efficacy of the treatment to induce weight loss, mice subchronically treated with T1AM (25mg/kg/day) show significant changes in gene expression. In liver we observed an increased expression of SIRT6 and GCK, and a decreased expression of SIRT4, whereas in adipose tissue only SIRT6 was increased. Since SIRT6 functions as a master gene regulator of glucose levels by maintaining the normal processes by which cells convert glucose into energy, whereas SIRT4 function as a negative regulator of fatty acids oxidative metabolism, these preliminary findings indicate that T1AM has a great potential to be used as a drug for the treatment of obesity.

(1) Klieverik LP et al., Journal of Endocrinology 2009; 201:377. (2) Haviland JA et al., Obesity Journal (in press).

Nothing to Disclose: FA, GC, RZ, MT, HR, TSS, SG, VC, DB

*Please take note of The Endocrine Society's News Embargo Policy at http://www.endo-society.org/endo2013/media.cfm