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. Materials and methods: We performed in silico analysis of 56 promoters to search for cis-cAMP (CREB) and cis-thyroid (IRE) 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 byT3. Conclusion: Our results point to other enzymes which may possibly be regulated byT3 and CREB, and speculate their joint roles in contributing to the optimal thermogenic acclimation. Arq Bras Endocrinol Metab. 2010;54(4):381-9