3-Iodothyronamine-mediated Metabolic Suppression in in vivo and in vitro Models: Potential Application to Emergency Medicine and Long-duration Spaceflights

Abstract

The goal of this article was to review the hypometabolic efficacy of 3-iodothyronamine (T1AM) in both in vivo and in vitro models from our past and current studies. T1AM is known to be a natural derivative of thyroid hormone. In the in vivo studies, a single-dose injection of T1AM to ICR mice decreased metabolic rate (MR) and body temperature by ~55% and 7℃, respectively, and lowered respiratory quotient from 0.85 to 0.7. Repeated injections of T1AM successfully induced two 2-d torpor bouts, separated by 1-d interbout arousal. In the in vitro studies, T1AM-treated C2C12 myotubes decreased the MR to 36%, and upregulated activation of AMP-activated protein kinase and acetyl-CoA carboxylase, but inhibited signaling activities associated with glycolytic activity. Thus, T1AM could induce hypometabolism in both the animal and cell models and promoted catabolism of lipid over carbohydrate as a fuel. For these outcomes closely mimic key features of true hibernators, T1AM may have potential applications to emergency medicine and long-term manned spaceflights.