TY  - JOUR
A1  - Münzner, Matthias
A1  - Tuvia, Neta
A1  - Deutschmann, Claudia
A1  - Witte, Nicole
A1  - Tolkachov, Alexander
A1  - Valai, Atijeh
A1  - Henze, Andrea
A1  - Sander, Leif E.
A1  - Raila, Jens
A1  - Schupp, Michael
T1  - Retinol-binding protein 4 and its membrane receptor STRA6 control adipogenesis by regulating cellular retinoid homeostasis and retinoic acid receptor alpha activity
JF  - Molecular and cellular biology
N2  - Retinoids are vitamin A (retinol) derivatives and complex regulators of adipogenesis by activating specific nuclear receptors, including the retinoic acid receptor (RAR) and retinoid X receptor (RXR). Circulating retinol-binding protein 4 (RBP4) and its membrane receptor STRA6 coordinate cellular retinol uptake. It is unknown whether retinol levels and the activity of RAR and RXR in adipocyte precursors are linked via RBP4/STRA6. Here, we show that STRA6 is expressed in precursor cells and, dictated by the apo-and holo-RBP4 isoforms, mediates bidirectional retinol transport that controls RAR alpha activity and subsequent adipocyte differentiation. Mobilization of retinoid stores in mice by inducing RBP4 secretion from the liver activated RAR alpha signaling in the precursor cell containing the stromal-vascular fraction of adipose tissue. Retinol-loaded holo-RBP4 blocked adipocyte differentiation of cultured precursors by activating RAR alpha. Remarkably, retinol-free apo-RBP4 triggered retinol efflux that reduced cellular retinoids, RAR alpha activity, and target gene expression and enhanced adipogenesis synergistically with ectopic STRA6. Thus, STRA6 in adipocyte precursor cells links nuclear RAR alpha activity to the circulating RBP4 isoforms, whose ratio in obese mice was shifted toward limiting the adipogenic potential of their precursors. This novel cross talk identifies a retinoldependent metabolic function of RBP4 that may have important implications for the treatment of obesity.
Y1  - 2013
U6  - https://doi.org/10.1128/MCB.00221-13
SN  - 0270-7306
SN  - 1098-5549
VL  - 33
IS  - 20
SP  - 4068
EP  - 4082
PB  - American Society for Microbiology
CY  - Washington
ER  -