Thermogenic effect of triiodothyroacetic acid at low doses in rat adipose tissue without adverse side effects in the thyroid axis.
Triiodothyroacetic acid (TRIAC) is a physiological product of triiodothyronine (T(3)) metabolism, with high affinity for T(3) nuclear receptors. Its interest stems from its potential thermogenic effects. Thus this work aimed 1) to clarify these thermogenic effects mediated by TRIAC vs. T(3) in vivo and 2) to determine whether they occurred predominantly in adipose tissues. To examine this, control rats were infused with equimolar T(3) or TRIAC doses (0.8 or 4 nmolx100 g body wt(-1) x day(-1)) or exposed for 48 h to cold. Both T(3) doses and only the highest TRIAC dose inhibited plasma and pituitary thyroid-stimulating hormone (TSH) and thyroxine (T(4)) in plasma and tissues. Interestingly, the lower TRIAC dose marginally inhibited plasma T(4). T(3) infusion increased plasma and tissue T(3) in a tissue-specific manner. The highest TRIAC dose increased TRIAC concentrations in plasma and tissues, decreasing plasma T(3). TRIAC concentrations in tissues were <10% those of T(3). Under cold exposure or high T(3) doses, TRIAC increased only in white adipose tissue (WAT). Remarkably, only the lower TRIAC dose activated thermogenesis, inducing ectopic uncoupling protein (UCP)-1 expression in WAT and maximal increases in UCP-1, UCP-2, and lipoprotein lipase (LPL) expression in brown adipose tissue (BAT), inhibiting UCP-2 in muscle and LPL in WAT. TRIAC, T(3), and cold exposure inhibited leptin secretion and mRNA in WAT. In summary, TRIAC, at low doses, induces thermogenic effects in adipose tissues without concomitant inhibition of TSH or hypothyroxinemia, suggesting a specific role regulating energy balance. This selective effect of TRIAC in adipose tissues might be considered a potential tool to increase energy metabolism.
Medina-Gomez
G
G
Instituto Investigaciones Biomedicas, Arturo Duperier, 4. 28029 Madrid, Spain.
Calvo
R M
RM
Obregon
M-J
MJ
D002001:Adipose Tissue, Brown / Q000187:drug effects* / Q000502:physiology; D052436:Adipose Tissue, White / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001833:Body Temperature Regulation / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects* / Q000502:physiology; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D007453:Iodide Peroxidase / Q000378:metabolism; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism; D020738:Leptin / Q000097:blood; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013961:Thyroid Gland / Q000187:drug effects* / Q000502:physiology; D013972:Thyrotropin / Q000097:blood; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology / Q000633:toxicity; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D000097564:Iodothyronine Deiodinase Type II
D007453:Iodide Peroxidase; D007473:Ion Channels; D020738:Leptin; D024101:Mitochondrial Proteins; D012333:RNA, Messenger; D013972:Thyrotropin; D013974:Thyroxine; D014284:Triiodothyronine; D000071256:Uncoupling Protein 1; D000071246:Uncoupling Protein 2; D000071247:Uncoupling Protein 3; D000097564:Iodothyronine Deiodinase Type II; C000604373:Ucp1 protein, rat; C000604391:Ucp2 protein, rat; C010642:3,3',5-triiodothyroacetic acid; C109812:iodothyronine deiodinase type I