Thyroxine 5'-deiodination mediates norepinephrine induced lipogenesis in dispersed brown adipocytes

Antonio C. Bianco, Suzy D. Carvalho, Celso R.F. Carvalho, Rogério Rabelo, Anselmo S. Moriscot

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Abstract

In euthyroid rats, maximal sympathetic nervous system stimulation (e.g. during cold exposure) results in a 3- to 4-fold increase in brown adipose tissue lipogenesis, a response that is blunted in hypothyroid rats. To further investigate this phenomenon, the role of local type II 5'-deiodinase (5'-DII) was studied in freshly isolated brown adipocytes. In a typical experiment, 1.5 x 106 cells were incubated for up to 48 h in a water- saturated 5% CO2-95% O2 atmosphere. After incubation with medium alone or with different concentrations of T4, T3, and/or norepinephrine (NE), lipogenesis was studied by measuring 1) the rate of fatty acid synthesis as reflected by 3H2O incorporation into lipids and 2) the activity of key rate-limiting enzymes, i.e. acetyl coenzyme A carhoxylase and malic enzyme, and the results are reported in terms of DNA content per tube. Lipogenesis decreased progressively over time (~40%) when no additions were made to the incubation medium. T4 or T3 partially prevented that inhibition at physiological concentrations (65 x 10-9 and 0.77 x 10 9 M, respectively), whereas a receptor-saturating concentration of T3 (154 x 10-9 M) doubled the lipogenesis rate. The addition of 10 6 M NE inhibited lipogenesis acutely (~50% by 12 h) and was followed by a progressive stimulation that reached ~2-fold by 48 h, but only in the presence of T4. Furthermore, NE did not attenuate T3 (154 x 10 9 M)-induced lipogenesis. Both the inhibition and the stimulation of lipogenesis caused by NE showed a strong dose-response relationship within the range of 10 11-10-5 M. The role of local 5'-DII was further tested by incubating brown adipocytes with 10 6 M NE and T4 (65 x 10-9 M) in the presence of 100 μM iopanoic acid, a potent inhibitor of 5'-DII. Although iopanoic acid did not affect the T3 stimulation of lipogenesis, it did block the ~2-fold stimulation of lipogenesis triggered by NE in the presence of T4, confirming the mediation of 5'-DII in this process. In conclusion, lipogenesis in brown adipose tissue is under complex hormonal control, with key roles played by NE, thyroid hormones, and local 5'-DII. As in other tissues, NE-generated signals acutely (12 h) inhibited lipogenesis. However, the presence of the 5'-DII generated enough T3 to stimulate lipogenesis and gradually reverse the short-lived NE- induced inhibition, leading to the 2- to 3-fold response observed at later time points.

Original languageEnglish (US)
Pages (from-to)571-578
Number of pages8
JournalEndocrinology
Volume139
Issue number2
DOIs
StatePublished - Jan 1 1998

ASJC Scopus subject areas

  • Endocrinology

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    Bianco, A. C., Carvalho, S. D., Carvalho, C. R. F., Rabelo, R., & Moriscot, A. S. (1998). Thyroxine 5'-deiodination mediates norepinephrine induced lipogenesis in dispersed brown adipocytes. Endocrinology, 139(2), 571-578. https://doi.org/10.1210/endo.139.2.5737