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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2018
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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. |
format | Online Article Text |
id | pubmed-5983833 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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