Endocrine Abstracts

3-Iodothyronamine (T₁AM) is a recently discovered compound which can be regarded as a novel hormone, since it is an endogenous relative of thyroid hormone with systemic distribution, which does not interact with thyroid hormone receptors, but rather with specific G protein-coupled receptors. T₁AM has been reported to modulate energy metabolism, and in rodents chronic T₁AM treatment has been associated with lipolysis and decreased body weight. To investigate the mechanism of this action we determined the effects of in vivo T₁AM administration on gene expression in rat adipose tissue and liver.

Eight Wistar rats were treated with T₁AM for five days (10 mg/kg per day by i.p. injection). The rats were sacrificed by guillotine and tissue samples were immediately removed and frozen in liquid nitrogen. Gene expression was evaluated by two-colour microarray analysis, using the whole rat genome G4131F microarrays (Agilent Technologies, Palo Alto, CA, USA). Significant differences in gene expression were confirmed by quantitative PCR.

In adipose tissue we detected 378 differentially expressed genes (DEGs), 268 up-regulated and 110 down-regulated, while in liver DEGs were 114 (63 up-regulated and 51 down-regulated). Functional analysis of microarray results revealed interesting interplays among DEGs. In adipose tissue pathway analysis provided evidence of decreased adipogenesis and stimulated lipolysis and fatty acid catabolism; modulated genes included acyl-CoA synthase 5, peroxisomal biogenesis factor 5, sirtuin 2, CCAAT/enhancer binding protein β (C/EBPβ) and the adiponectin receptor PAQR3. In liver most of the differentially expressed genes were of unknown function but glycerol kinase and malic enzyme were inhibited.

We conclude that in vivo T₁AM administration produced significant transcriptional effects, which are expected to stimulate lipid catabolism and induce a reduction of fatty mass. These actions might therefore provide the basis for the reported effectiveness of T₁AM as a lipolytic agent.