Control of mitochondrial metabolism and systemic energy homeostasis by microRNAs 378 and 378

摘要: Obesity and metabolic syndrome are associated with mitochondrial dysfunction deranged regulation of genes. Peroxisome proliferator-activated receptor γ coactivator 1β (PGC-1β) is a transcriptional that regulates metabolism biogenesis through stimulation nuclear hormone receptors other transcription factors. We report the PGC-1β gene encodes two microRNAs (miRNAs), miR-378 miR-378*, which counterbalance actions PGC-1β. Mice genetically lacking miR-378* resistant to high-fat diet-induced obesity exhibit enhanced fatty acid elevated oxidative capacity insulin-target tissues. Among many targets these miRNAs, carnitine O-acetyltransferase, enzyme involved in metabolism, MED13, component Mediator complex controls activity, repressed by respectively, livers miR-378/378* KO mice. Consistent as contributors previous studies have implicated O-acetyltransferase MED13 obesity. Our findings identify integral components regulatory circuit functions under conditions stress control systemic energy homeostasis overall insulin target Thus, miRNAs provide potential for pharmacologic intervention syndrome.