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

Autor: Leonardo Lorenzini, Alessandro Saba, Riccardo Zucchi, Martina Sabatini, Grazia Chiellini, Hannah Reiland, Marco Tonelli, Micheal Rogowski, Vittoria Carnicelli, Sandra Ghelardoni, Fariba M. Assadi-Porter, Ebru S. Selen Alpergin
Rok vydání: 2018
Předmět:
0301 basic medicine
obesity
White adipose tissue
Germinal Center Kinases
lcsh:Chemistry
Mice
Thyronines
Glycolysis
lcsh:QH301-705.5
Spectroscopy
chemistry.chemical_classification
3-iodothyronamine
metabolomics
glucose and lipid metabolism
sirtuins
biology
Fatty Acids
Computer Science Applications1707 Computer Vision and Pattern Recognition
General Medicine
3. Good health
Computer Science Applications
Adipose Tissue
Liver
Sirtuin
3-Iodothyronamine
Glucose and lipid metabolism
Metabolomics
Obesity
Sirtuins
Catalysis
Molecular Biology
Physical and Theoretical Chemistry
Organic Chemistry
Inorganic Chemistry
Female
SIRT6
medicine.medical_specialty
Carbohydrate metabolism
Protein Serine-Threonine Kinases
Article
Mitochondrial Proteins
03 medical and health sciences
Internal medicine
medicine
Animals
Fatty acid
Lipid metabolism
Metabolic pathway
030104 developmental biology
Endocrinology
Glucose
chemistry
lcsh:Biology (General)
lcsh:QD1-999
biology.protein
Anti-Obesity Agents
Zdroj: International Journal of Molecular Sciences
International Journal of Molecular Sciences, Vol 19, Iss 5, p 1535 (2018)
International Journal of Molecular Sciences; Volume 19; Issue 5; Pages: 1535
ISSN: 1422-0067
Popis: 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.
Databáze: OpenAIRE
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