Retinol saturase (all-trans-retinol 13,14-reductase) (RETSAT)

Retinol saturase (RETSAT) is an endoplasmic reticulum membrane-bound oxidoreductase enzyme that catalyzes the reduction of the 13–14 double bond in all-trans-retinol, producing 13,14-dihydroretinol and related dihydroretinoids[1][2]. RETSAT is under transcriptional control of PPARγ and is robustly upregulated during adipogenesis, playing a critical role in adipocyte differentiation and normal lipid accumulation[3]. RETSAT modulates lipid metabolism both in adipose tissue and the liver, and regulates cellular responses to oxidative stress by promoting reactive oxygen species (ROS) and lipid peroxide formation[1]. Its expression is reduced in obesity (in part due to macrophage infiltration) and can be restored by thiazolidinedione treatment[3]. In cancer, particularly pancreatic ductal adenocarcinoma, RETSAT is highly expressed in hypoxic tumor regions and promotes replication stress resistance and chemoresistance[2]. In the intestine, RETSAT modulates epithelial homeostasis and inflammatory responses, impacting fat mass accumulation and protection from colitis[2]. RETSAT thus integrates retinoid metabolism, adipose tissue development, metabolic homeostasis, oxidative stress regulation, and cancer cell adaptation to stress.

Other names

All-trans-retinol 13,14-reductasePPSIGUNQ439/PRO872RetSatFLJ20296All-trans-13,14-dihydroretinol saturasePPAR-alpha-regulated and starvation-induced gene protein

For thiazolidinediones: Indirect upregulation of RETSAT enzyme via PPARγ activation, promoting adipogenesis and metabolic regulation[3] For gemcitabine: Resistance via RETSAT-mediated support of replication fork restarting in cancer cells[2]