RESUMO
Our study elucidates functional roles for conserved cis- elements associated with the evolution of mammalian hibernation. Genomic analyses found topologically associated domains (TADs) that disproportionately accumulated convergent genomic changes in hibernators, including the TAD for the Fat Mass & Obesity ( Fto ) locus. Some hibernation-linked cis- elements in this TAD form regulatory contacts with multiple neighboring genes. Knockout mice for these cis- elements exhibit Fto, Irx3, and Irx5 gene expression changes, impacting hundreds of genes downstream. Profiles of pre-torpor, torpor, and post-torpor phenotypes found distinct roles for each cis- element in metabolic control, while a high caloric diet uncovered different obesogenic effects. One cis- element promoting a lean phenotype influences foraging behaviors throughout life, affecting specific behavioral sequences. Thus, convergent evolution in hibernators pinpoints functional genetic mechanisms of mammalian metabolic control. One-sentence summary: Deletions of conserved cis- elements tied to hibernator evolution causes diverse metabolic traits in mice.
RESUMO
Elucidating the genetic basis of mammalian metabolism could help define mechanisms central to health and disease. Here, we define conserved cis- regulatory elements (CREs) and programs for mammalian metabolic control. We delineate gene expression and chromatin responses in the mouse hypothalamus for 7 steps of the Fed-to-Fasted-to-Refed (FFR) response process. Comparative genomics of hibernating versus non-hibernating lineages then illuminates cis- elements showing convergent changes in hibernators. Hibernators accumulated loss-of-function effects for specific CREs regulating hypothalamic FFR responses. Multi-omics approaches pinpoint key CREs, genes, regulatory programs, and cell types in the divergence of hibernating and homeothermic lineages. The refeeding period after extended fasting is revealed as one critical period of chromatin remodeling with convergent genomic changes. This genetic framework is a step toward harnessing hibernator adaptations in medicine. One sentence summary: Convergent signals define cis- regulatory mechanisms behind food scarcity responses and hibernator-homeotherm divergence.
RESUMO
Resumen Los resultados de las investigaciones sobre cannabis medicinal han traído a las mesas de gobierno discusiones sobre su potencial terapéutico y las medidas a tomar para controlar su producción, comercialización y utilización. En Colombia, desde el 2017, el mercado del cannabis medicinal se encuentra regulado; sin embargo, existen brechas entre la norma, disponibilidad y acceso de los pacientes a productos farmacéuticos con derivados del cannabis, aprobados por el ente regulatorio y que cumplan con los estándares de calidad. Desde esta perspectiva, se considera necesario que el gobierno nacional lidere, en coordinación con la academia y el sector productivo, el desarrollo de preparados farmacéuticos a base de cannabis; además de establecer e implementar medidas estratégicas y concertadas, orientadas a mejorar el acceso y la utilización adecuada de los productos farmacéuticos de cannabis medicinal, en especial para los casos en los que se pueda establecer una clara relación riesgo/beneficio. Con ello, se contribuye a mejorar las condiciones de salud de pacientes que se pueden beneficiar de estas opciones, al igual que al desarrollo y consolidación de un sector promisorio para el país. MÉD. UIS.2020;33(1):53-8.
Abstract The results of medical marijuana research have brought to the government tables discussions about their therapeutic potential and the measures to be taken to control their production, commercialization and use. In Colombia, since 2017, the medical cannabis market is regulated; however, there are gaps between the laws, availability and the access of patients to pharmaceutical products with cannabis derivatives approved by the regulatory entity and that comply with the standards of quality. From this perspective, it is necessary for the national government to lead, in coordination with the academy and the productive sector, the development of pharmaceutical preparations based on cannabis and to establish and implement strategic and concerted measures, aimed to improve access and proper use of medical marijuana pharmaceutical products, mainly for cases in which a clear risk/benefit relationship can be established. This would help to improve the health conditions of patients who can get benefits from these options, as well as the development and consolidation of a promising sector for the country. MÉD.UIS.2020;33(1):53-8.
