Project description:The GEMINAL Study- Gene Expression Modulation by Intervention with Nutrition and Lifestyle We conducted a pilot study to examine changes in gene expression in men diagnosed with low risk prostate cancer who participated in an intensive nutrition and lifestyle intervention. We profiled gene expression in morphologically normal tissues from prostate biopsies of all 30 participants before and after the intervention. Keywords: Differential gene expression analysis Pre-intervention versus Post-Intervention
Project description:The GEMINAL Study- Gene Expression Modulation by Intervention with Nutrition and Lifestyle We conducted a pilot study to examine changes in gene expression in men diagnosed with low risk prostate cancer who participated in an intensive nutrition and lifestyle intervention. We profiled gene expression in morphologically normal tissues from prostate biopsies of all 30 participants before and after the intervention. Keywords: Differential gene expression analysis
Project description:The objective of this study was to examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles. Substantial weight loss (-15.2+3.8%) in lifestyle participants was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes related to immune function and inflammatory responses involving endothelial activation. In contrast, participants losing minimal weight (-3.1+2.5%) showed only minor changes in cardiovascular risk factors and markers of inflammation, and no changes in gene expression compared to non-intervention controls after 1 year. Weight loss (>10%) during lifestyle modification is associated with down-regulation of genetic pathways governing interactions between circulating immune cells and the vascular endothelium and may be required to successfully reduce CVD risk. A prospective nonrandomized trail was conducted over 1 year in participants undergoing intensive lifestyle modification to reverse or stabilize progression of coronary artery disease. Cardiovascular risk factors, inflammatory biomarkers, and gene expression as a function of weight loss were assessed in 89 lifestyle participants and 71 retrospectively matched controls undergoing usual care.
Project description:Weight loss and physical activity are the cornerstones of therapy for type 2 diabetes. However, providing an effective lifestyle intervention is difficult because of limited availability of reliable programs, patient inconvenience, and cost. A worksite setting provides a unique opportunity for lifestyle therapy because it reduces these barriers. We conducted an 8-month randomized controlled trial in persons with obesity and diabetes to determine the therapeutic effects and potential mechanisms of intensive-lifestyle-therapy (energy restriction and supervised exercise training) conducted at the worksite. Intensive-lifestyle-therapy resulted in marked (17%) weight loss, associated with beneficial changes in body composition, cardiorespiratory fitness, muscle strength, glycemic control, β-cell function and insulin sensitivity in the liver, adipose tissue, and skeletal muscle, despite a decrease in diabetes medication use. These beneficial effects were associated with changes in skeletal muscle (increased metabolite content and expression of genes involved in NAD biosynthesis, sirtuin signaling, and mitochondrial biogenesis and function), adipose tissue (decreased expression of genes involved in extracellular matrix remodeling), and a major plasma mediator of insulin resistance (decreased plasma PAI-1). These findings demonstrate that effective intensive-lifestyle-therapy can be implemented at the worksite, and has profound therapeutic, clinical, physiological, and cellular effects in people with obesity and type 2 diabetes.
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: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=96.3±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, estimated by an oral glucose tolerance test and the Matsuda Index, increased 29.2% post intervention (2.4±0.3 to 3.1±0.3, 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 change≥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.
Project description:There is a need to understand genetic and lifestyle factors that may influence the risk of cancer progression in men who have organ-confined prostate cancer and have chosen a programme of 'active surveillance' as opposed to radical treatment with the associated health risks. Epidemiological studies have suggested that consumption of cruciferous vegetables is associated with reduced risk of developing aggressive prostate cancer. In this study we recruited men on active surveillance for low- to intermediate-risk prostate cancer to determine whether a 12-month dietary intervention can elicit transcriptional or nmetabolic responses in their prostate that would be consistent with a reduction in the risk of progression. We undertook RNAseq on prostate biopsies collected before and after a 12-month intervention with broccoli soups.
Project description:The objective of this study was to examine relationships between weight loss through changes in lifestyle and peripheral blood gene expression profiles. Substantial weight loss (-15.2+3.8%) in lifestyle participants was associated with improvement in selected cardiovascular risk factors and significant changes in peripheral blood gene expression from pre- to post-intervention: 132 unique genes showed significant expression changes related to immune function and inflammatory responses involving endothelial activation. In contrast, participants losing minimal weight (-3.1+2.5%) showed only minor changes in cardiovascular risk factors and markers of inflammation, and no changes in gene expression compared to non-intervention controls after 1 year. Weight loss (>10%) during lifestyle modification is associated with down-regulation of genetic pathways governing interactions between circulating immune cells and the vascular endothelium and may be required to successfully reduce CVD risk.
Project description:This is a TMT-labeled proteomics analysis of human skeletal muscle specimens obtained from the following groups: older adult controls, critical limb ischemia patients undergoing surgical intervention, and critical limb ischemia patients undergoing limb amputation.