Disclosure: The authors declare competing financial interests. Authors F.M.A.P., D.E.B., M.T., and W.P.P. are cofounders of Isomark LLC.
NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1AM treatment
Article first published online: 29 MAY 2013
Copyright © 2013 The Obesity Society
Volume 21, Issue 12, pages 2538–2544, December 2013
How to Cite
Haviland, J.A., Reiland, H., Butz, D.E., Tonelli, M., Porter, W.P., Zucchi, R., Scanlan, T.S., Chiellini, G. and Assadi-Porter, F.M. (2013), NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1AM treatment. Obesity, 21: 2538–2544. doi: 10.1002/oby.20391
Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author notes may be found in the online version of this article.
Funding agencies: This research was supported by the Rodale Foundation, the Farmers Advocating for Organics (FAFO) fund, grant R01 DC009018 from NIH, and the Wisconsin Institute of Discovery Grant (WID-135A039). This work was supported in part by funds from the following: the Rodale Foundation; the Farmers Advocating for Organics (FAFO) fund to W.P.P.; grants R01 DC009018 from NIH; the Wisconsin Institute of Discovery Grant (WID-135A039) to F.M.A.P. This study made use of the National Magnetic Resonance Facility at Madison, which is supported by NIH grants P41RR02301 (BRTP/ NCRR) and P41GM66326 (NIGMS). Additional equipment was purchased with funds from the University of Wisconsin, the NIH (RR02781, RR08438), the NSF (DMB-8415048, OIA-9977486, BIR-9214394), and the USDA.
- Issue published online: 3 DEC 2013
- Article first published online: 29 MAY 2013
- Accepted manuscript online: 20 MAR 2013 02:13AM EST
- Manuscript Accepted: 9 JAN 2013
- Manuscript Revised: 8 JAN 2013
- Manuscript Received: 8 NOV 2012
- The Rodale Foundation
- The Farmers Advocating for Organics (FAFO) fund. Grant Number: R01 DC009018 from NIH
- The Wisconsin Institute of Discovery Grant. Grant Number: WID-135A039
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.
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 T1AM on weight maintenance.
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.