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A novel role of 3‐iodothyronamine (T1AM) as a master regulator of lipid and glucose metabolism through activating sirtuins 4 and 6 genes (373.7)
Author(s) -
AssadiPorter Fariba,
Tonelli Marco,
Chiellini Grazia
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.373.7
Subject(s) - endocrinology , medicine , regulator , adipose tissue , lipolysis , metabolism , lipid metabolism , gene expression , biology , carbohydrate metabolism , gene , biochemistry
Objectives: T 1 AM subchronic low doses cause rapid lipolysis and weight loss with no change in food consumption. We investigated tissue specific effects of T 1 AM, a natural thyroid hormone analog, on metabolic pathways and associated transcriptional gene signaling and protein profiles. Methods: Three groups (n=5), randomly selected spontaneously obese female CD ‐1 mice were injected once daily for 7 days with saline, 10 mg/kg T1AM, or 25 mg/kg T 1 AM. Blood drawn on days ‐3, 4, and 7, was analyzed by 1 H‐NMR. Mice were sacrificed on day 7 and the organs collected for real‐time PCR and protein profiles. Results: Multivariate analysis of the 1 H‐NMR data revealed increased 3‐hydroxybutyrate and acetate and no differences in plasma glucose levels in T 1 AM‐treated vs. control mice, . Mice treated with high dose T 1 AM show significant changes in tissue specific gene expression. The livers had increased expression of SIRT6 and GCK, and decreased expression of SIRT4, but in adipose tissue only SIRT6 increased. Protein expression studies confirmed over‐expression of SIRT6 and GCK in liver. Conclusions: SIRT6 functions as a master gene regulator of glucose levels by maintaining the normal cell processes converting glucose into energy, SIRT4 functions as a negative regulator of fatty acids oxidative metabolism. Our results indicate that T 1 AM can act as a master regulator of both glucose and fat metabolism in obese mice. Grant Funding Source : Supported by NIH/NIDCD (R01DC009818)