It has also been shown recently that RORa controls LEE011 adipocyte differentiation. Our present data showing that the expression of G6PC, which encodes a subunit of G6Pase, is controlled by RORa in HepG2 cells are in agreement with a study showing that G6PC is a RORa target gene in mouse liver. They agree with the fact that G6Pase is regulated by Rev-erba. Our results support the notion that RORa may play a role in controlling the carbohydrate metabolism, besides its function in lipid metabolism. G6Pase is a key enzyme in the regulation of hepatic glucose production and blood glucose homeostasis. It catalyzes the terminal step in the glycogenolytic and gluconeogenic pathways. Mutations in the G6PC gene result in glycogen storage disease type 1a mainly characterized by hypoglycemia. Tight links between G6Pase and the insulin regulatory pathway have been reported. ADIPOQ, which encodes a protein also Axitinib involved in both lipid and glucose metabolism has also been identified as a RORa target in this study. That RORa and HIF-1a regulate each other under hypoxic stress further supports a role for RORa in carbohydrate metabolism since it is well known that the carbohydrate metabolism pathway is greatly altered during the hypoxic stress. All these data argue in favor of a new role for RORa in controlling carbohydrate metabolism. We show that the SPARC gene, also known as Osteonectin is a new RORa target gene. This gene encodes a matricellular protein that controls cell-cell and cell-matrix adhesion. It may also play a role in cell growth and, depending on the cell type, this multi-faceted protein is associated with a highly aggressive tumor phenotype or behaves as a tumor suppressor. In hepatocellular carcinomas, SPARC expression correlates with tumor angionenesis. Expression of the SPARC gene is upregulated in fibrotic liver while its down regulation by adenoviral expression of an antisense SPARC attenuates liver fibrosis. Interestingly, SPARC over-expression in hepatocellular carcinoma cells results in a reduced tumorigenicity. Another gene that we found up-regulated by RORa is HEPN1, which encodes a peptide involved in the control of cell growth and apoptosis, and whose expression is down-regulated in hepatocellular carcinoma. These data strongly suggest a role for RORa at different steps of liver carcinogenesis. In conclusion, our results point to possible roles of the RORa nuclear receptor in liver cells. They also open new routes to think about a more general role for RORa in physiology. Normal aging is associated with a decline in cognitive function, reduced neural plasticity, and is a primary risk factor for many neurodegenerative diseases including Alzheimer��s disease.