Journal
OBESITY
Volume 21, Issue 12, Pages 2538-2544Publisher
WILEY
DOI: 10.1002/oby.20391
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Funding
- Rodale Foundation
- Farmers Advocating for Organics (FAFO) fund
- NIH [R01 DC009018, P41RR02301, P41GM66326, RR02781, RR08438]
- Wisconsin Institute of Discovery Grant [WID-135A039]
- University of Wisconsin
- NSF [DMB-8415048, OIA-9977486, BIR-9214394]
- USDA
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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 T1AM 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.
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