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Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression

Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metaboli...

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Autores principales: Assadi-Porter, Fariba M., Reiland, Hannah, Sabatini, Martina, Lorenzini, Leonardo, Carnicelli, Vittoria, Rogowski, Micheal, Selen Alpergin, Ebru S., Tonelli, Marco, Ghelardoni, Sandra, Saba, Alessandro, Zucchi, Riccardo, Chiellini, Grazia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983833/
https://www.ncbi.nlm.nih.gov/pubmed/29786646
http://dx.doi.org/10.3390/ijms19051535
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author Assadi-Porter, Fariba M.
Reiland, Hannah
Sabatini, Martina
Lorenzini, Leonardo
Carnicelli, Vittoria
Rogowski, Micheal
Selen Alpergin, Ebru S.
Tonelli, Marco
Ghelardoni, Sandra
Saba, Alessandro
Zucchi, Riccardo
Chiellini, Grazia
author_facet Assadi-Porter, Fariba M.
Reiland, Hannah
Sabatini, Martina
Lorenzini, Leonardo
Carnicelli, Vittoria
Rogowski, Micheal
Selen Alpergin, Ebru S.
Tonelli, Marco
Ghelardoni, Sandra
Saba, Alessandro
Zucchi, Riccardo
Chiellini, Grazia
author_sort Assadi-Porter, Fariba M.
collection PubMed
description Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways. In liver, we observed an increased gene and protein expression of Sirt6 (a master gene regulator of glucose) and Gck (glucose kinase) and a decreased expression of Sirt4 (a negative regulator of fatty acids oxidation (FAO)), whereas in white adipose tissue only Sirt6 was increased. Metabolomics analysis supported physiological changes at both doses with most increases in FAO, glycolysis indicators and the mitochondrial substrate, at the highest dose of T1AM. Together our results suggest that T1AM acts through sirtuin-mediated pathways to metabolically reprogram fatty acid and glucose metabolism possibly through small molecules signaling. Our novel mechanistic findings indicate that T1AM has a great potential as a drug for the treatment of obesity and possibly diabetes.
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spelling pubmed-59838332018-06-05 Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression Assadi-Porter, Fariba M. Reiland, Hannah Sabatini, Martina Lorenzini, Leonardo Carnicelli, Vittoria Rogowski, Micheal Selen Alpergin, Ebru S. Tonelli, Marco Ghelardoni, Sandra Saba, Alessandro Zucchi, Riccardo Chiellini, Grazia Int J Mol Sci Article Obesity is a complex disease associated with environmental and genetic factors. 3-Iodothyronamine (T1AM) has revealed great potential as an effective weight loss drug. We used metabolomics and associated transcriptional gene and protein expression analysis to investigate the tissue specific metabolic reprogramming effects of subchronic T1AM treatment at two pharmacological daily doses (10 and 25 mg/kg) on targeted metabolic pathways. Multi-analytical results indicated that T1AM at 25 mg/kg can act as a novel master regulator of both glucose and lipid metabolism in mice through sirtuin-mediated pathways. In liver, we observed an increased gene and protein expression of Sirt6 (a master gene regulator of glucose) and Gck (glucose kinase) and a decreased expression of Sirt4 (a negative regulator of fatty acids oxidation (FAO)), whereas in white adipose tissue only Sirt6 was increased. Metabolomics analysis supported physiological changes at both doses with most increases in FAO, glycolysis indicators and the mitochondrial substrate, at the highest dose of T1AM. Together our results suggest that T1AM acts through sirtuin-mediated pathways to metabolically reprogram fatty acid and glucose metabolism possibly through small molecules signaling. Our novel mechanistic findings indicate that T1AM has a great potential as a drug for the treatment of obesity and possibly diabetes. MDPI 2018-05-22 /pmc/articles/PMC5983833/ /pubmed/29786646 http://dx.doi.org/10.3390/ijms19051535 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Assadi-Porter, Fariba M.
Reiland, Hannah
Sabatini, Martina
Lorenzini, Leonardo
Carnicelli, Vittoria
Rogowski, Micheal
Selen Alpergin, Ebru S.
Tonelli, Marco
Ghelardoni, Sandra
Saba, Alessandro
Zucchi, Riccardo
Chiellini, Grazia
Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression
title Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression
title_full Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression
title_fullStr Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression
title_full_unstemmed Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression
title_short Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression
title_sort metabolic reprogramming by 3-iodothyronamine (t1am): a new perspective to reverse obesity through co-regulation of sirtuin 4 and 6 expression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5983833/
https://www.ncbi.nlm.nih.gov/pubmed/29786646
http://dx.doi.org/10.3390/ijms19051535
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