Modulation of gene expression by 3-iodothyronamine: genetic evidence for a lipolytic pattern.
3-Iodothyronamine (T1AM) is an endogenous biogenic amine, structurally related to thyroid hormone, which is regarded as a novel chemical messenger. The molecular mechanisms underlying T1AM effects are not known, but it is possible to envisage changes in gene expression, since delayed and long-lasting phenotypic effects have been reported, particularly with regard to the modulation of lipid metabolism and body weight. To test this hypothesis we analysed gene expression profiles in adipose tissue and liver of eight rats chronically treated with T1AM (10 mg/Kg twice a day for five days) as compared with eight untreated rats. In vivo T1AM administration produced significant transcriptional effects, since 378 genes were differentially expressed in adipose tissue, and 114 in liver. The reported changes in gene expression are expected to stimulate lipolysis and beta-oxidation, while inhibiting adipogenesis. T1AM also influenced the expression of several genes linked to lipoprotein metabolism suggesting that it may play an important role in the regulation of cholesterol homeostasis. No effect on the expression of genes linked to toxicity was observed. The assay of tissue T1AM showed that in treated animals its endogenous concentration increased by about one order of magnitude, without significant changes in tissue thyroid hormone concentration. Therefore, the effects that we observed might have physiological or pathophysiological importance. Our results provide the basis for the reported effectiveness of T1AM as a lipolytic agent and gain importance in view of a possible clinical use of T1AM in obesity and/or dyslipidaemia.
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Veronica
V
Mariotti
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Erika
E
Melissari
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Caterina
C
Iofrida
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Marco
M
Righi
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Manuela
M
Di Russo
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Riccardo
R
Donzelli
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Alessandro
A
Saba
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Sabina
S
Frascarelli
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Grazia
G
Chiellini
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Riccardo
R
Zucchi
Department of Surgical, Medical, Molecular Pathology and of Critical Care, University of Pisa, Pisa, Italy.
Silvia
S
Pellegrini
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects*; D008066:Lipolysis / Q000187:drug effects* / Q000235:genetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013970:Thyronines / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
C487948:3-iodothyronamine; D013970:Thyronines