Sabina Lorca

Learn More
RATIONALE Oxidative myofibers in the skeletal muscles express high levels of angiogenic factors, have dense vasculature, and promptly revascularize during ischemia. Estrogen-related receptor-gamma (ERRγ) activates genes that govern metabolic and vascular features typical to oxidative myofibers. Therefore, ERRγ-dependent remodeling of the myofibers may(More)
Treatment of Duchenne muscular dystrophy (DMD) by replacing mutant dystrophin or restoring dystrophin-associated glycoprotein complex (DAG) has been clinically challenging. Instead, identifying and targeting muscle pathways deregulated in DMD will provide new therapeutic avenues. We report that the expression of nuclear receptor estrogen-related receptor-γ(More)
Dissecting exercise-mimicking pathways that can replicate the benefits of exercise in obesity and diabetes may lead to promising treatments for metabolic disorders. Muscle estrogen-related receptor gamma (ERRγ) is induced by exercise, and when over-expressed in the skeletal muscle mimics exercise by stimulating glycolytic-to-oxidative myofiber switch,(More)
How type I skeletal muscle inherently maintains high oxidative and vascular capacity in the absence of exercise is unclear. We show that nuclear receptor ERRγ is highly expressed in type I muscle and, when transgenically expressed in anaerobic type II muscles (ERRGO mice), dually induces metabolic and vascular transformation in the absence of exercise.(More)
Rapamycin at high doses (2-10 mg/kg body weight) inhibits mammalian target of rapamycin complex 1 (mTORC1) and protein synthesis in mice. In contrast, low doses of rapamycin (10 μg/kg) increase mTORC1 activity and protein synthesis in skeletal muscle. Similar changes are found with SLF (synthetic ligand for FKBP12, which does not inhibit mTORC1) and in mice(More)
Revascularization of ischemic skeletal muscle is governed by a balance between pro- and antiangiogenic factors in multiple cell types but particularly in myocytes and endothelial cells. Whereas the regulators of proangiogenic factors are well defined (e.g., hypoxia-inducible factor [HIF]), the transcriptional pathways encoding antiangiogenic factors remain(More)
Skeletal muscle wasting is prevalent in many chronic diseases, necessitating inquiries into molecular regulation of muscle mass. Nuclear receptor co-activator peroxisome proliferator-activated receptor co-activator 1 alpha (PGC1α) and its splice variant PGC1α4 increase skeletal muscle mass. However, the effect of the other PGC1 sub-type, PGC1β, on muscle(More)
Aryl Hydrocarbon Receptor Nuclear Translocator/ hypoxia-inducible factor 1 beta (ARNT/ HIF1β), a member of bHLH-PAS family of transcriptional factors, plays a critical role in metabolic homeostasis, insulin resistance and glucose intolerance. The contributions of ARNT in pancreas, liver and adipose tissue to energy balance through gene regulation have been(More)
Rationale: Oxidative myofibers in the skeletal muscles express high levels of angiogenic factors, have dense vasculature, and promptly revascularize during ischemia. Estrogen-related receptor-gamma (ERR ) activates genes that govern metabolic and vascular features typical to oxidative myofibers. Therefore, ERR -dependent remodeling of the myofibers may(More)
  • 1