RESUMEN
Adaptive thermogenesis is essential for survival, and therefore is tightly regulated by a central neural circuit. Here, we show that microRNA (miR)-33 in the brain is indispensable for adaptive thermogenesis. Cold stress increases miR-33 levels in the hypothalamus and miR-33-/- mice are unable to maintain body temperature in cold environments due to reduced sympathetic nerve activity and impaired brown adipose tissue (BAT) thermogenesis. Analysis of miR-33f/f dopamine-ß-hydroxylase (DBH)-Cre mice indicates the importance of miR-33 in Dbh-positive cells. Mechanistically, miR-33 deficiency upregulates gamma-aminobutyric acid (GABA)A receptor subunit genes such as Gabrb2 and Gabra4. Knock-down of these genes in Dbh-positive neurons rescues the impaired cold-induced thermogenesis in miR-33f/f DBH-Cre mice. Conversely, increased gene dosage of miR-33 in mice enhances thermogenesis. Thus, miR-33 in the brain contributes to maintenance of BAT thermogenesis and whole-body metabolism via enhanced sympathetic nerve tone through suppressing GABAergic inhibitory neurotransmission. This miR-33-mediated neural mechanism may serve as a physiological adaptive defense mechanism for several stresses including cold stress.
Asunto(s)
MicroARNs/metabolismo , Sistema Nervioso Simpático/fisiología , Termogénesis/genética , Tejido Adiposo Pardo/fisiología , Animales , Temperatura Corporal/fisiología , Peso Corporal , Encéfalo/metabolismo , Línea Celular , Frío , Dieta Alta en Grasa , Estrés del Retículo Endoplásmico , Humanos , Integrasas/metabolismo , Masculino , Ratones , Ratones Obesos , MicroARNs/genética , Consumo de Oxígeno/fisiología , Fenotipo , Subunidades de Proteína/genética , Subunidades de Proteína/metabolismo , Receptores de GABA-A/genética , Receptores de GABA-A/metabolismoRESUMEN
Recently, advances in genomic technology such as RNA sequencing and genome-wide profiling have enabled the identification of considerable numbers of non-coding RNAs (ncRNAs). MicroRNAs have been studied for decades, leading to the identification of those with disease-causing and/or protective effects in vascular disease. Although other ncRNAs such as long ncRNAs have not been fully described yet, recent studies have indicated their important functions in the development of vascular diseases. Here, we summarize the current understanding of the mechanisms and functions of ncRNAs, focusing on microRNAs, circular RNAs and long ncRNAs in vascular diseases.
Asunto(s)
ARN no Traducido/metabolismo , Enfermedades Vasculares/metabolismo , Humanos , ARN no Traducido/genética , Enfermedades Vasculares/genéticaRESUMEN
No effective treatment is yet available to reduce infarct size and improve clinical outcomes after acute myocardial infarction by enhancing early reperfusion therapy using primary percutaneous coronary intervention. The study showed that Kyoto University Substance 121 (KUS121) reduced endoplasmic reticulum stress, maintained adenosine triphosphate levels, and ameliorated the infarct size in a murine cardiac ischemia and reperfusion injury model. The study confirmed the cardioprotective effect of KUS121 in a porcine ischemia and reperfusion injury model. These findings confirmed that KUS121 is a promising novel therapeutic agent for myocardial infarction in conjunction with primary percutaneous coronary intervention.
