NMR‐based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1AM treatment. (29th May 2013)

• Record Type: Journal Article
• 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.
• Is Part Of: Obesity. Volume 21:Number 12(2013:Dec.)
• Page Start: 2538
• Page End: 2544
• Publication Date: 2013-05-29
• Subjects: Obesity -- Periodicals; 616.398005
• DOI: 10.1002/oby.20391
• Languages: English
• ISSNs: 1930-7381

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="oby20391-sec-0001" sec-type="section"> <title>Objective</title> <p>3‐Iodothyronamine (T<sub>1</sub>AM), an analog of thyroid hormone, is a recently discovered fast‐acting endogenous metabolite. Single high‐dose treatments of T<sub>1</sub>AM have produced rapid short‐term effects, including a reduction of body temperature, bradycardia, and hyperglycemia in mice.</p> </sec> <sec id="oby20391-sec-0002" sec-type="section"> <title>Design and Methods</title> <p>The effect of daily low doses of T<sub>1</sub>AM (10 mg/kg) for 8 days on weight loss and metabolism in spontaneously overweight mice was monitored. The experiments were repeated twice (<italic>n</italic> = 4). Nuclear magnetic resonance (NMR) spectroscopy of plasma and real‐time analysis of exhaled <sup>13</sup>CO<sub>2</sub> in breath by cavity ring down spectroscopy (CRDS) were used to detect T<sub>1</sub>AM‐induced lipolysis.</p> </sec> <sec id="oby20391-sec-0003" sec-type="section"> <title>Results</title> <p>CRDS detected increased lipolysis in breath shortly after T<sub>1</sub>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 T<sub>1</sub>AM include both lipolysis and protein breakdown. After discontinuation of T<sub>1</sub>AM treatment, mice regained only 1.8% of the lost weight in the following 2 weeks, indicating lasting effects of T<sub>1</sub>AM on weight maintenance.</p> </sec> <sec id="oby20391-sec-0004" sec-type="section"> <title>Conclusions</title> <p>CRDS in combination with NMR and <sup>13</sup>C‐metabolic tracing constitute a powerful method of investigation in obesity studies for identifying <italic>in vivo</italic> biochemical pathway shifts and unanticipated debilitating side effects.</p> </sec> </abstract>