NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T₁AM treatment

Objective 3-Iodothyronamine (T₁AM), an analog of thyroid hormone, is a recently discovered fast-acting endogenous metabolite. Single high-dose treatments of T₁AM have produced rapid short-term effects, including a reduction of body temperature, bradycardia, and hyperglycemia in mice. Design and Methods The effect of daily low doses of T₁AM (10 mg/kg) for 8 days on weight loss and metabolism in spontaneously overweight mice was monitored. The experiments were repeated twice (n = 4). Nuclear magnetic resonance (NMR) spectroscopy of plasma and real-time analysis of exhaled ¹³CO₂ in breath by cavity ring down spectroscopy (CRDS) were used to detect T₁AM-induced lipolysis. Results CRDS detected increased lipolysis in breath shortly after T₁AM administration that was associated with a significant weight loss but independent of food consumption. NMR spectroscopy revealed alterations in key metabolites in serum: valine, glycine, and 3-hydroxybutyrate, suggesting that the subchronic effects of T₁AM include both lipolysis and protein breakdown. After discontinuation of T₁AM treatment, mice regained only 1.8% of the lost weight in the following 2 weeks, indicating lasting effects of T ₁AM on weight maintenance. Conclusions CRDS in combination with NMR and ¹³C-metabolic tracing constitute a powerful method of investigation in obesity studies for identifying in vivo biochemical pathway shifts and unanticipated debilitating side effects.