Retinoic acid has different effects on UCP1 expression in mouse and human adipocytes

Abstract

BackgroundIncreased adipose thermogenesis is being considered as a strategy aimed at preventing or reversing obesity. Thus, regulation of the uncoupling protein 1 (UCP1) gene in human adipocytes is of significant interest. Retinoic acid (RA), the carboxylic acid form of vitamin A, displays agonist activity toward several nuclear hormone receptors, including RA receptors (RARs) and peroxisome proliferator-activated receptor δ (PPARδ). Moreover, RA is a potent positive regulator of UCP1 expression in mouse adipocytes.ResultsThe effects of all-trans RA (ATRA) on UCP1 gene expression in models of mouse and human adipocyte differentiation were investigated. ATRA induced UCP1 expression in all mouse white and brown adipocytes, but inhibited or had no effect on UCP1 expression in human adipocyte cell lines and primary human white adipocytes. Experiments with various RAR agonists and a RAR antagonist in mouse cells demonstrated that the stimulatory effect of ATRA on UCP1 gene expression was indeed mediated by RARs. Consistently, a PPARδ agonist was without effect. Moreover, the ATRA-mediated induction of UCP1 expression in mouse adipocytes was independent of PPARγ coactivator-1α.ConclusionsUCP1 expression is differently affected by ATRA in mouse and human adipocytes. ATRA induces UCP1 expression in mouse adipocytes through activation of RARs, whereas expression of UCP1 in human adipocytes is not increased by exposure to ATRA.

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“…Oil Red O staining and immunoblotting for hormone-sensitive lipase (HSL) confirmed the robust differentiation using the protocol employed (Supplementary Fig. 1), in congruence with our previous reports 29,30 . Based on the in vivo expression levels and cold-induced changes (Fig.…”

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“…1). The gene expression changes were consistent with previously published data confi rming that SGBS preadipocyte differentiation is a reproducible model for the study of human adipogenesis ( 12,(37)(38)(39)(40).…”

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“…Retinoic acid administration in vivo increases UCP1 mRNA and protein expression in WAT depots in mice [250,251], which is associated with antiobesity and antidiabetic effects in vivo [251]. Retinoic acid administration to cultured adipocytes (3T3-L1 adipocytes, C3H10T1/2 adipocytes, or MEFs) during differentiation also increases UCP1 mRNA expression [250,251], through a p38 MAPK-mediated mechanism [252] that is independent of PGC-1␣ [253]. While both of these studies agree that activation of RAR is involved, as the increase in UCP1 mRNA can be achieved with the RAR agonist TTNPB [250,251], Mercader et al were also able to increase UCP1 mRNA expression with the RXR agonist methoprene [252], although Berry et al found no effect with the RXR-specific agonist 9cis-retinoic acid [251].…”