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Increases in insulin sensitivity among obese youth are associated with gene expression changes in whole blood.

ABSTRACT: 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. 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 eight significant pathways identified, including insulin signaling, type 1 diabetes, and glycerophospholipid metabolism. Participants with increased insulin sensitivity exhibited five times the number of significant genes altered compared with nonresponders (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.

SUBMITTER: Miranda DN

PROVIDER: S-EPMC4008712 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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Increases in insulin sensitivity among obese youth are associated with gene expression changes in whole blood.

Miranda Danielle N DN Coletta Dawn K DK Mandarino Lawrence J LJ Shaibi Gabriel Q GQ

Obesity (Silver Spring, Md.) 20140218 5

<h4>Objective</h4>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.<h4>Methods</h4>Fifteen (7M/8F) overweight/obese (BMI percentile = 96.3 ± 1.1) Latino adolescents (15.0 ± 0.9 years) completed a 12-week lifestyle ...[more]

PMID: 24470352

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Project description:Lifestyle intervention can improve insulin sensitivity in obese youth yet few studies have examined the biological mechanisms underlying improvements. Therefore, the purpose of this study was to explore biological pathways associated with intervention-induced improvements in insulin sensitivity. Fifteen (7M/8F) overweight/obese (BMI percentile=96.3M-BM-11.1) Latino adolescents (15.0M-BM-10.9 years) completed a 12-week lifestyle intervention that included weekly nutrition education and 180 minutes of moderate-vigorous exercise per week. Insulin sensitivity, estimated by an oral glucose tolerance test and the Matsuda Index, increased 29.2% post intervention (2.4M-BM-10.3 to 3.1M-BM-10.3, p=0.01). 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. A total of 1,459 probes corresponding to mRNA transcripts (717 up, 742 down) were differentially expressed with a fold changeM-bM-^IM-%1.2 and P<0.05. Among the genes identified were hexokinase 3 (HK3), ATPase, H+ transporting V0 subunit e2 (ATPV0E), and sterol regulatory element binding transcription factor 1 (SREBF1), and endothelial cell adhesion molecule (ESAM). There were 8 pathways identified that met the criteria for significance, 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). These findings offer insight into the molecular mechanisms underlying health improvements among high-risk Latino youth. Lifestyle interventions may contribute to improved insulin sensitivity through pathways related to insulin signaling and immune response. Further, genetic factors may mediate response to lifestyle intervention. Fifteen (7M/8F) overweight/obese Latino Youth Whole blood RNA samples evaluated pre and post intervention.

Project description:BACKGROUND:Obesity and pubertal insulin resistance worsen cardiovascular (CV) risk factors in youth. It is unclear how the relationships of obesity and insulin resistance with CV risk compare to adults. SUBJECTS AND METHODS:We evaluated 66 pubertal youth (mean?±?SD: age 14.2 ± 2.0?years, body mass index [BMI] 36.6 ± 6.0 kg/m2 , hemoglobin A1c [HbA1c] 38.5 ± 6.1 mmol/mol) and 355 adults with comparable BMI (age 52.7 ± 9.4?years, BMI 35.1 ± 5.1 kg/m2 , HbA1c 39.8 ± 4.2 mmol/mol) participating in a multicenter study. Insulin sensitivity was quantified using hyperglycemic clamps. Assessment of CV risk factors was standardized across sites. Regression analyses compared the impact of insulin sensitivity and CV risk factors between youth and adults. RESULTS:Obese pubertal youth were more insulin resistant than comparably obese adults (P <?.001), but with similar slopes for the inverse relationship between insulin sensitivity and obesity. The impact of obesity on CV risk factors was explained by insulin sensitivity (P =?NS after adjustment for sensitivity). The two age groups did not differ in relationships between insulin sensitivity and diastolic blood pressure, total cholesterol, and low-density lipoprotein (LDL) cholesterol, after adjusting for obesity. However, while systolic blood pressure (SBP) and high-density lipoprotein (HDL) cholesterol exhibited the expected direct and inverse relationships, respectively with insulin sensitivity in adults, these slopes were flat in youth across the range of insulin sensitivity (P ??.05 for group differences). CONCLUSIONS:Effects of obesity on CV risk factors were attributable to insulin sensitivity in both groups. The relationships between insulin sensitivity and CV risk factors were similar in obese youth and adult groups except for SBP and HDL cholesterol. CLINICAL TRIAL REGISTRATION:The RISE consortium studies are registered through Clinicaltrials.gov as NCT01779362 (Adult Medication Study); NCT01763346 (Adult Surgery Study); and NCT01779375 (Pediatric Medication Study). Clinical trial registration numbers: NCT01779362, NCT01779375 and NCT01763346 at clinicaltrials.gov.

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Increases in insulin sensitivity among obese youth are associated with gene expression changes in whole blood.

Publications

Increases in insulin sensitivity among obese youth are associated with gene expression changes in whole blood.

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