Endocrine Abstracts

Iodothyronamines are endogenous trace amines which are putative products of thyroid hormone decarboxylation by Aromatic Amino acid Decarboxylase (AADC). 3-Iodothyronamine (T₁AM) has been shown to have profound effects on rodents in vivo, including reductions in body temperature, blood pressure and cardiac output, alongside a switch from carbohydrate to fat utilisation. It is possible that T₁AM induces some of these effects by activating a member of the Trace Amine-Associated Receptor (TAAR) GPCR family, TAAR1. We are interested in possible non-genomic effects of thyroid hormones and this study investigates the mechanism proposed above and the possible role of T₁AM in fat metabolism in adipose tissue.

We have shown, using RT-PCR with rat TAAR1-specific primers, that TAAR1 mRNA is present in various rat tissues, including adipose. To further investigate the role of TAAR1 activation in fat metabolism, we used mouse 3T3-L1 adipocyte cultures. Fat content is reduced in these cells when insulin is withdrawn and the rate of fat depletion is elevated by around 20–30% over 2–6 days when tyramine (a known ligand for TAAR1) is present at 10 μM. Quantitative measurement of fat content was performed using the fluorescent reagent Adipored (Cambrex). Western Blot analysis indicates that Hormone Sensitive Lipase (HSL) is phosphorylated at the Protein Kinase A (PKA) target site Ser 563 in the presence of tyramine or T₁AM at 10 μM. This suggests that T₁AM could instigate lipolysis through activation of TAAR1, leading to downstream cAMP accumulation, activation of PKA and subsequent phosphorylation of HSL. This stimulation of lipolysis would help support the observed shift in whole-body fuel utilisation from carbohydrate to fat after T₁AM administration.