title: Norepinephrine, tri-iodothyronine and insulin upregulate glyceraldehyde-3-phosphate dehydrogenase mRNA during Brown adipocyte differentiation.
abstract: Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) gene expression was studied in differentiating brown adipocytes. Northern blot analysis showed that GAPDH mRNA levels increased during differentiation of precursor cells into mature adipocytes, mainly in the initial stages of the differentiation process. Insulin, tri-iodothyronine (T(3)) and norepinephrine, the main regulators of brown adipose tissue function, upregulated GAPDH mRNA levels, whereas retinoic acid inhibited them. The effect of insulin was present on all culture days examined, was time- and dose-dependent, and was exerted through its own receptors, as demonstrated by comparing insulin and insulin-like growth factor (IGF)-I and -II potencies in this system. Using the transcriptional inhibitor, actinomycin D, we demonstrated that T(3), and to a lesser extent insulin, stabilized GAPDH mRNA. Experiments with cycloheximide indicated that both hormones require de novo protein synthesis to achieve their effects. Using cAMP analogs, we showed that the effect of norepinephrine is probably exerted through this second messenger. Co-operation was elucidated between norepinephrine- and insulin-mediated induction of GAPDH mRNA levels. In summary, we have demonstrated that GAPDH mRNA is subjected to multifactorial regulation in differentiating brown adipocytes that includes differentiation of precursor cells and the lipogenic/lipolytic regulators of the tissue.
authors.affiliation: Instituto de Investigaciones Biomédicas 'Alberto Sols', Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Arturo Duperier 4, E-28029-Madrid, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Barroso
authors.forename: B
authors.initials: B
authors.lastname: Benito
authors.forename: C
authors.initials: C
authors.lastname: Garcí-Jiménez
authors.forename: A
authors.initials: A
authors.lastname: Hernández
authors.forename: M J
authors.initials: MJ
authors.lastname: Obregón
authors.forename: P
authors.initials: P
authors.lastname: Santisteban
mesh_terms: D002001:Adipose Tissue, Brown / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000187:drug effects / Q000235:genetics*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism* / Q000494:pharmacology; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014212:Tretinoin / Q000378:metabolism; D014284:Triiodothyronine / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007328:Insulin; D012333:RNA, Messenger; D014284:Triiodothyronine; D014212:Tretinoin; D000242:Cyclic AMP; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases; D009638:Norepinephrine