Enhancing T3 and cAMP responsive gene participation in the thermogenic regulation of fuel oxidation pathways.
OBJECTIVE
We sought to identify glycolysis, glycogenolysis, lipolysis, Krebs cycle, respiratory chain, and oxidative phosphorylation enzymes simultaneously regulated by T3 and cAMP.


METHODS
We performed in silico analysis of 56 promoters to search for cis-cAMP (CREB) and cis-thyroid (TRE) response elements, considering UCP1, SERCA2 and glyceraldehyde 3-phosphate dehydrogenase as reference. Only regulatory regions with prior in vitro validation were selected.


RESULTS
29/56 enzymes presented potential TREs in their regulatory sequence, and some scored over 0.80 (better predictive value 1): citrate synthase, phosphoglucose isomerase, succinate dehydrogenases A/C, UCP3, UCP2, UCP4, UCP5, phosphoglycerate mutase, glyceraldehyde 3-P dehydrogenase, glucokinase, malate dehydrogenase, acyl-CoA transferase (thiolase), cytochrome a3, and lactate dehydrogenase. Moreover, some enzymes have not yet been described in the literature as genomically regulated by T3.


CONCLUSIONS
Our results point to other enzymes which may possibly be regulated by T3 and CREB, and speculate their joint roles in contributing to the optimal thermogenic acclimation.
Dorsa
Karina Kores
KK
Universidade Federal de São Paulo, São Paulo, SP, Brazil.
Santos
Michelle Venâncio dos
MV
Silva
Magnus R Dias da
MR
D000242:Cyclic AMP / Q000235:genetics*; D004798:Enzymes / Q000378:metabolism; D006801:Humans; D010085:Oxidative Phosphorylation; D022722:Thermogenesis / Q000235:genetics*; D014284:Triiodothyronine / Q000235:genetics*
D004798:Enzymes; D014284:Triiodothyronine; D000242:Cyclic AMP