| First Author | Rosell M | Year | 2012 |
| Journal | Endocrinology | Volume | 153 |
| Issue | 3 | Pages | 1162-73 |
| PubMed ID | 22253419 | Mgi Jnum | J:182546 |
| Mgi Id | MGI:5315822 | Doi | 10.1210/en.2011-1367 |
| Citation | Rosell M, et al. (2012) Peroxisome proliferator-activated receptors-alpha and -gamma, and cAMP-mediated pathways, control retinol-binding protein-4 gene expression in brown adipose tissue. Endocrinology 153(3):1162-73 |
| abstractText | Retinol binding protein-4 (RBP4) is a serum protein involved in the transport of vitamin A. It is known to be produced by the liver and white adipose tissue. RBP4 release by white fat has been proposed to induce insulin resistance. We analyzed the regulation and production of RBP4 in brown adipose tissue. RBP4 gene expression is induced in brown fat from mice exposed to cold or treated with peroxisome proliferator-activated receptor (PPAR) agonists. In brown adipocytes in culture, norepinephrine, cAMP, and activators of PPARgamma and PPARalpha induced RBP4 gene expression and RBP4 protein release. The induction of RBP4 gene expression by norepinephrine required intact PPAR-dependent pathways, as evidenced by impaired response of the RBP4 gene expression to norepinephrine in PPARalpha-null brown adipocytes or in the presence of inhibitors of PPARgamma and PPARalpha. PPARgamma and norepinephrine can also induce the RBP4 gene in white adipocytes, and overexpression of PPARalpha confers regulation by this PPAR subtype to white adipocytes. The RBP4 gene promoter transcription is activated by cAMP, PPARalpha, and PPARgamma. This is mediated by a PPAR-responsive element capable of binding PPARalpha and PPARgamma and required also for activation by cAMP. The induction of the RBP4 gene expression by norepinephrine in brown adipocytes is protein synthesis dependent and requires PPARgamma-coactivator-1-alpha, which acts as a norepinephine-induced coactivator of PPAR on the RBP4 gene. We conclude that PPARgamma- and PPARalpha-mediated signaling controls RBP4 gene expression and releases in brown adipose tissue, and thermogenic activation induces RBP4 gene expression in brown fat through mechanisms involving PPARgamma-coactivator-1-alpha coactivation of PPAR signaling. |
