title: NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T(1)AM treatment.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Zoology, University of Wisconsin-Madison, Madison, Wisconsin, USA.
authors.forename: J A
authors.initials: JA
authors.lastname: Haviland
authors.forename: H
authors.initials: H
authors.lastname: Reiland
authors.forename: D E
authors.initials: DE
authors.lastname: Butz
authors.forename: M
authors.initials: M
authors.lastname: Tonelli
authors.forename: W P
authors.initials: WP
authors.lastname: Porter
authors.forename: R
authors.initials: R
authors.lastname: Zucchi
authors.forename: T S
authors.initials: TS
authors.lastname: Scanlan
authors.forename: G
authors.initials: G
authors.lastname: Chiellini
authors.forename: F M
authors.initials: FM
authors.lastname: Assadi-Porter
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000097:blood; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001944:Breath Tests; D004044:Dietary Proteins / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005998:Glycine / Q000097:blood; D008066:Lipolysis / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D055432:Metabolomics; D051379:Mice; D009765:Obesity / Q000188:drug therapy; D013970:Thyronines / Q000008:administration & dosage*; D014633:Valine / Q000097:blood; D015431:Weight Loss / Q000187:drug effects*
chemical_list: C487948:3-iodothyronamine; D004044:Dietary Proteins; D013970:Thyronines; D014633:Valine; D005998:Glycine; D020155:3-Hydroxybutyric Acid