Increases in Insulin Sensitivity among Obese Youth are Associated with Gene Expression Changes in Whole Blood

OBJECTIVE: Lifestyle intervention can improve insulin sensitivity in obese youth yet few studies have examined the molecular signatures associated with these improvements. Therefore, the purpose of this study was to explore gene expression changes in whole-blood that are associated with intervention-induced improvements in insulin sensitivity. DESIGN AND METHODS: Fifteen (7M/8F) overweight/obese (BMI percentile=96.3±1.1) Latino adolescents (15.0±0.9 years) completed a 12-week lifestyle intervention that included weekly nutrition education and 180 minutes of moderate-vigorous exercise per week. Insulin sensitivity was estimated by an oral glucose tolerance test and the Matsuda Index. Global microarray analysis profiling from whole blood was performed to examine changes in gene expression and to explore biological pathways that were significantly changed in response to the intervention. RESULTS: A total of 1,459 probes corresponding to mRNA transcripts (717 up, 742 down) were differentially expressed with a fold change ≥1.2. These genes were mapped within 8 significant pathways identified, including insulin signaling, type 1 diabetes, and glycerophospholipid metabolism. Participants that increased insulin sensitivity exhibited five times the number of significant genes altered compared to non-responders (1,144 vs. 230). CONCLUSIONS: These findings suggest that molecular signatures from whole blood are associated with lifestyle-induced health improvements among high-risk Latino youth.