OBJECTIVE: @entity2690 resistance (IR) is a hallmark of @entity28 and @entity209 . 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 @entity1 cohort. RESEARCH DESIGN AND METHODS: We measured circulating plasma ex-RNAs in 2,317 @entity1 without @entity6 in the Framingham Heart Study (FHS) Offspring Cohort at cycle 8 and defined associations between ex-RNAs and IR (measured by circulating @entity2690 level). We measured association between candidate ex-RNAs and markers of @entity1386 . Sensitivity analyses included individuals with @entity6 . In a separate cohort of 90 overweight/ @entity28 youth, we measured selected ex-RNAs and metabolites. Biology of candidate microRNAs was investigated in silico. RESULTS: The mean age of FHS @entity1 was 65.8 years (56% female), with average BMI 27.7 kg/m(2); @entity1 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). @entity2853 was associated with IR and regional @entity1386 in adults and IR in @entity1 (independent of metabolites). Pathway analysis revealed metabolic regulatory roles for @entity2853 , including regulation of IR pathways ( @entity33725 , target of @entity3446 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.

Extracellular RNAs Are Associated With XXXX Resistance and Metabolic Phenotypes.

@entity1 :: ('9606', 'Species') :: ['participants', 'children', 'human'] @entity6 :: ('MESH:D003920', 'Disease') :: ['diabetes'] @entity28 :: ('MESH:D009765', 'Disease') :: ['obese', 'obesity'] @entity2690 :: ('3630', 'Gene') :: ['Insulin', 'insulin'] @entity2853 :: ('406906', 'Gene') :: ['miR-122'] @entity3446 :: ('MESH:D020123', 'Chemical') :: ['rapamycin'] @entity209 :: ('MESH:D008659', 'Disease') :: ['metabolic disease'] @entity33725 :: ('5563', 'Gene') :: ['AMPK'] @entity1386 :: ('MESH:D018205', 'Disease') :: ['adiposity']
@entity2690 :: (3630,Gene) :: ['Insulin']
