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Extracellular RNAs Are Associated With Insulin Resistance and Metabolic Phenotypes

OBJECTIVE: Insulin resistance (IR) is a hallmark of obesity and metabolic disease. Circulating extracellular RNAs (ex-RNAs), stable RNA molecules in plasma, may play a role in IR, though most studies on ex-RNAs in IR are small. We sought to characterize the relationship between ex-RNAs and metabolic...

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Detalles Bibliográficos
Autores principales: Shah, Ravi, Murthy, Venkatesh, Pacold, Michael, Danielson, Kirsty, Tanriverdi, Kahraman, Larson, Martin G., Hanspers, Kristina, Pico, Alexander, Mick, Eric, Reis, Jared, de Ferranti, Sarah, Freinkman, Elizaveta, Levy, Daniel, Hoffmann, Udo, Osganian, Stavroula, Das, Saumya, Freedman, Jane E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Diabetes Association 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5360281/
https://www.ncbi.nlm.nih.gov/pubmed/28183786
http://dx.doi.org/10.2337/dc16-1354
Descripción
Sumario:OBJECTIVE: Insulin resistance (IR) is a hallmark of obesity and metabolic disease. Circulating extracellular RNAs (ex-RNAs), stable RNA molecules in plasma, may play a role in IR, though most studies on ex-RNAs in IR are small. We sought to characterize the relationship between ex-RNAs and metabolic phenotypes in a large community-based human cohort. RESEARCH DESIGN AND METHODS: We measured circulating plasma ex-RNAs in 2,317 participants without diabetes in the Framingham Heart Study (FHS) Offspring Cohort at cycle 8 and defined associations between ex-RNAs and IR (measured by circulating insulin level). We measured association between candidate ex-RNAs and markers of adiposity. Sensitivity analyses included individuals with diabetes. In a separate cohort of 90 overweight/obese youth, we measured selected ex-RNAs and metabolites. Biology of candidate microRNAs was investigated in silico. RESULTS: The mean age of FHS participants was 65.8 years (56% female), with average BMI 27.7 kg/m(2); participants in the youth cohort had a mean age of 15.5 years (60% female), with mean BMI 33.8 kg/m(2). In age-, sex-, and BMI-adjusted models across 391 ex-RNAs in FHS, 18 ex-RNAs were associated with IR (of which 16 were microRNAs). miR-122 was associated with IR and regional adiposity in adults and IR in children (independent of metabolites). Pathway analysis revealed metabolic regulatory roles for miR-122, including regulation of IR pathways (AMPK, target of rapamycin signaling, and mitogen-activated protein kinase). CONCLUSIONS: These results provide translational evidence in support of an important role of ex-RNAs as novel circulating factors implicated in IR.