Norepinephrine, tri-iodothyronine and insulin upregulate glyceraldehyde-3-phosphate dehydrogenase mRNA during brown adipocyte differentiation

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studie d in differentiating brown adipocytes, Northern blot analysis showed that G APDH mRNA levels increased during differentiation of precursor cells into m ature adipocytes, mainly in the initial stages of the differentiation proce ss. Insulin, tri-iodothyronine (T-3) and norepinephrine, the main regulator s of brown adipose tissue function, upregulated GAPDH mRNA levels, whereas retinoic acid inhibited them. The effect of insulin was present on all cult ure days examined, was time- and dose-dependent, and was exerted through it s own receptors, as demonstrated by comparing insulin and insulin-like grow th factor (IGF)-I and -II potencies in this system. Using the transcription al inhibitor, actinomycin D, we demonstrated that T-3, and to a lesser exte nt insulin, stabilized GAPDH mRNA, Experiments with cycloheximide indicated that both hormones require de novo protein synthesis to achieve their effe cts. Using cAMP analogs, we showed that the effect of norepinephrine is pro bably exerted through this second messenger. Go-operation was elucidated be tween norepinephrine- and insulin-mediated induction of GAPDH mRNA levels. In summary, rye have demonstrated that GAPDH mRNA is subjected to multifact orial regulation in differentiating brown adipocytes that includes differen tiation of precursor cells and the lipogenic/lipolytic regulators of the ti ssue.