Retinol metabolism impacts fat regulation

RBP4 acts as a transport protein for delivering Vitamin A (retinol) to tissues and has a role in adipocyte differentiation. Recently, scientists discovered that stimulated by retinoic acid gene 6 (stra6) was the membrane receptor for RBP4 when mediating cellular retinol uptake. Also, an enzyme called retinol saturase (RetSat) promotes adipocyte differentiation through retinol metabolism.

The STRA6 (The function of the RBP4 receptor stra6 during retinol saturase regulated adipocyte differentiation) initiative is investigating if stra6 is the link between RBP4 and RetSat in facilitating adipocyte differentiation. Besides stra6 gain- and loss-of-function studies, researchers will also study components involved in transcriptional regulation of stra6 with a focus on peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is the target of certain antidiabetic drugs and targeting components of this pathway could prove therapeutically effective.

During the first project phase researchers made considerable progress in elucidating factors involved in transcriptional regulation of stra6. In obese mice, they found altered stra6 expression in the adipose tissue.

Gain- and loss-of-function studies revealed that stra6 expression at the cell membrane positively regulates differentiation of the 3T3-L1 adipocyte cell line. Key insights were obtained into factors affecting adipocyte differentiation, insulin signalling and lipid accumulation.

Project outcomes were presented at international conferences and published in the prestigious peer-reviewed journal Molecular and Cellular Biology.

A better understanding of factors involved in retinol metabolism and fat regulation could reveal novel therapeutic targets in the RBP4/stra6/RetSat axis for effectively addressing metabolic diseases. This could enhance EU competitiveness in the pharma and nutraceutical sectors.