NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T(1)AM treatment

• Published in: Obesity (Silver Spring, Md.) Vol. 21; no. 12; p. 2538
• Main Authors: Haviland, J A, Reiland, H, Butz, D E, Tonelli, M, Porter, W P, Zucchi, R, Scanlan, T S, Chiellini, G, Assadi-Porter, F M
• Format: Journal Article
• Language: English
• Published: United States 01.12.2013
• Subjects: 3-Hydroxybutyric Acid - blood; Animals; Body Weight - drug effects; Breath Tests; Dietary Proteins - metabolism; Dose-Response Relationship, Drug; Female; Glycine - blood; Lipolysis - drug effects; Magnetic Resonance Spectroscopy; Metabolomics; Mice; Obesity - drug therapy; Thyronines - administration & dosage; Valine - blood; Weight Loss - drug effects
• ISSN: 1930-739X
• DOI: 10.1002/oby.20391

3-Iodothyronamine (T1 AM), an analog of thyroid hormone, is a recently discovered fast-acting endogenous metabolite. Single high-dose treatments of T1 AM have produced rapid short-term effects, including a reduction of body temperature, bradycardia, and hyperglycemia in mice. The effect of daily low doses of T1 AM (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 (13) CO2 in breath by cavity ring down spectroscopy (CRDS) were used to detect T1 AM-induced lipolysis. CRDS detected increased lipolysis in breath shortly after T1 AM 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 T1 AM include both lipolysis and protein breakdown. After discontinuation of T1 AM treatment, mice regained only 1.8% of the lost weight in the following 2 weeks, indicating lasting effects of T1 AM on weight maintenance. CRDS in combination with NMR and (13) C-metabolic tracing constitute a powerful method of investigation in obesity studies for identifying in vivo biochemical pathway shifts and unanticipated debilitating side effects.