Linking pathways and processes: Retinoic acid and glucose

Abstract This chapter focuses on the interplay between retinoids and carbohydrate metabolisms. Retinoic acid (RA), an active retinoid, is intracellularly synthesized by two-step conversion of retinol and activates transcription of target genes mainly through retinoic acid receptor (RAR). On the other hand, glucose is oxidized to produce ATP, but if in excess, it is stored effectively as triacylglycerol by activating nutrient-sensing transcription factors (TFs) such as carbohydrate response element-binding protein (ChREBP), sterol response element-binding protein (SREBP), and liver X receptor (LXR). Expression of these TFs is induced by hepatocyte nuclear factor (HNF)4α and peroxisome proliferator-activated receptor (PPAR)γ. It is reported that RA represses expression of HNF4α directly and of PPARγ indirectly. RA also induces small heterodimer partner expression that inhibits activity of TFs such as HNF4α and LXR. Therefore RA may control carbohydrate metabolism through repressing upstream TFs (nuclear receptors) that activate expression of the nutrient-sensing TFs.