Potent thermogenic action of triiodothyroacetic acid in brown adipocytes

Triiodothyroacetic acid (TRIAC) is a triiodothyronine (T3) metabolite with high affinity for T3 nuclear receptors. We compared the thermogenic action of TRIAC versus T3 in brown adipocytes, by studying target genes known to mediate thermogenic action: uncoupling protein 1 (UCP-1), a marker of brown adipocytes, and type II-5'deiodinase (D2), which provides the T3 required for thermogenesis. TRIAC is 10-50 times more potent than T3 at increasing the adrenergic induction of UCP-1 mRNA and D2 activities. TRIAC action on UCP-1 is exerted at the transcriptional level. In the presence of an adrenergic stimulus, TRIAC is also more potent than T3, inducing lipoprotein lipase mRNA and 5 deiodinase (D3) activity and mRNA. Maximal effects occur at very low concentrations (0.2 nM). The greater potency of TRIAC is not due to preferential cellular or nuclear uptake. Therefore, TRIAC is a potent thermogenic agent that might increase energy expenditure and regulate T3 production in brown adipocytes.