Retinoid-related orphan receptor   regulates several genes that control metabolism in skeletal muscle cells: links to modulation of reactive oxygen species production

Abstract

Retinoid-related orphan receptor g (RORg) is an orphan nuclear hormone receptor (NR) that is preferentially expressed in skeletal muscle and several other tissues, including pancreas, thymus, prostate, liver and testis. Surprisingly, the specific role of RORg in skeletal muscle, a peripheral tissue, has not been examined. Muscle is one of the most energy demanding tissues which accounts for w40% of the total body mass and energy expenditure, O75% of glucose disposal and relies heavily on b-oxidation of fatty acids. We hypothesize that RORg regulates metabolism in this major mass lean tissue. This hypothesis was examined by gain and loss of function studies in an in vitro mouse skeletal muscle cell culture model. We show that RORg mRNA and protein are dramatically induced during skeletal muscle cell differentiation. We utilize stable ectopic over-expression of VP16-RORg (gain of function), native RORg and RORgDH12 (loss of function) vectors to modulate RORg mRNA expression and function. Ectopic VP16 (herpes simplex virus transcriptional activator)-RORg and native RORg expression increases RORa mRNA expression. Candidate-driven expression profiling of lines that ectopically express the native and variant forms of RORg suggested that this orphan NR has a function in regulating the expression of genes that control lipid homeostasis (fatty acid-binding protein 4, CD36 (fatty acid translocase), lipoprotein lipase and uncoupling protein 3), carbohydrate metabolism (GLUT5 (fructose transporter), adiponectin receptor 2 and interleukin 15 (IL-15)) and muscle mass . Surprisingly, the investigation revealed a function for RORg in the pathway that regulates production of reactive oxygen species.

Effect of Peucedanum japonicum Thunb on the Expression of Obesity-Related Genes in Mice on a High-Fat Diet

“…The specific functions of this protein are not fully understood. However, a study in mouse skeletal muscle cells suggested that RORC increased the expression of the retinoid-related orphan receptor alpha RORα gene, and thereby modulated the expression of genes involved in the control of lipid homeostasis, such as fatty acid binding protein, fatty acid translocase, lipoprotein lipase, and uncoupling protein 3 21 .…”

Regulation of the fructose transporter GLUT5 in health and disease

“…GLUT5 is expressed in skeletal muscle of human (14,40,41,66,71,81,125,137,143,144), rat (40), and mouse (131). In fact, GLUT5 is, along with GLUT4 and GLUT12, one of the more significantly expressed GLUTs in human skeletal muscle compared with the other members of the GLUT family (144).…”

Cloning and expression analysis of two ROR-γ homologues (ROR-γa1 and ROR-γa2) in rainbow trout Oncorhynchus mykiss

“…In fish a weak expression of this gene in cardiac muscle and somites has been reported in zebrafish larvae, as well as in the brain [8]. The role of ROR-g in these organs is still unclear, but it has been suggested that it is involved in the regulation of muscle metabolism and growth control [37]. When analysing the expression of ROR-g in trout cell lines and primary cultures, it was found that this gene was highly expressed in the fibroblast-like cell lines.…”