Obesity-associated Gene Expression Research Articles

Adapting Random Forests to Predict Obesity-Associated Gene Expression.

Random forests (RFs) are effective at predicting gene expression from genotype data. However, a comparison of RF regressors and classifiers, including feature selection and encoding, has been under-explored in the context of gene expression prediction. Specifically, we examine the role of ordinal or one-hot encoding and of data balancing via oversam-pling in the prediction of obesity-associated gene expression. Our work shows that RFs compete with PrediXcan in the prediction of obesity-associated gene expression in subcutaneous adipose tissue, a highly relevant tissue to obesity. Additionally, RFs generate predictions for obesity-associated genes where PrediXcan fails to do so.

Fat mass and obesity-associated gene expression and disease severity in type 2 diabetes mellitus

Obesity and visceral adiposity are major risk factors for type 2 diabetes mellitus (T2DM). The fat mass and obesity-associated (FTO) gene is associated with increased risk of obesity and T2DM. The aim of this work was to study the association between FTO gene expression and serum FTO protein level with disease severity in T2DM patients. Patients and methodsOne hundred T2DM patients were divided into two equal groups according to diabetes control and complications and fifty healthy controls were included in this study. FTO messenger ribonucleic acid (mRNA) expression level was analyzed by Real time polymerase chain reaction (PCR) technique and serum level of FTO protein was measured by ELISA. ResultsFTO gene expression and FTO protein levels were increased in the two T2DM groups compared to the control group with significant further increases in patients with severe disease. FTO gene expression and FTO protein levels were positively correlated with obesity, insulin resistance and blood glucose indices as well as the presence of diabetic complications. Regression analyses showed that FTO gene expression and FTO protein levels were risk factors for T2DM severity. ConclusionsIncreased FTO gene expression and its serum protein levels are associated with increased T2DM severity.

Do Health Promoting Compounds of Flaxseed Attenuate Weight Gain Via Modulation of Obesity Gene Expression?

Diet-induced obesity (DIO) has been shown to increase DNA methyltransferases (DNMTs) expression and DNMTs binding at obesity-associated genes. Natural compounds have the potential to reverse obesity-associated gene expression via the regulation of DNA methylation. The objective of this study was to determine the effect of health promoting compounds of flaxseed on DNMTs and obesity-associated gene expression and weight gain. Sixty C57BL/6J male mice were randomly assigned into one of the following diet groups and fed for eight weeks: 45% kcal fat; 45% kcal fat+10% whole flaxseed; 45% kcal fat+6% defatted flaxseed; 45% kcal fat+4% flaxseed oil; and 16% kcal fat. DNMT1, DNMT3a, DNMT3b, leptin, and peroxisome proliferator-activated receptor (PPAR)-α expressions in adipose and muscle tissues were determined by real-time PCR. The health promoting compounds of flaxseed affected selected gene expression and attenuated weight gain. Further research is needed to identify the specific mechanisms modulating leptin or PPAR-α expression during DIO development.

Dietary Carbohydrate Promotes Cell Survival in Cancer Via the Up-Regulation of Fat Mass and Obesity-Associated Gene Expression Level.

Cancer cells are mainly dependent on glycolysis for their growth and survival. Dietary carbohydrates play a critical role in the growth and proliferation of cancer and a low-carbohydrate diet may help slow down the growth of tumours. However, the exact mechanisms behind this effect are unclear. This review study aimed to investigate the effect of fat mass and obesity-associated (FTO) gene in the association between dietary carbohydrates and cancer. This study was carried out using keywords such as polymorphism and/or cancer and/or dietary carbohydrate and/or FTO gene. PubMed and Science Direct databases were used to collect all related articles published from 1990 to 2018.Recent studies showed that the level of FTO gene expression in cancer cells is dramatically increased and may play a role in the growth of these cells through the regulation of the cellular metabolic pathways, including the phosphoinositide 3-kinases/protein kinaseB (PI3K/AKT) signaling pathway. Dietary carbohydrate may influence the FTO gene expression by eliminating the inhibitory effect of adenosine monophosphate-activated protein kinase (AMPK) on the FTO gene expression. This review summarised what has been recently discovered about the effects of dietary carbohydrate on cancer cells and tried to determine the mediating role of the FTO gene in these effects.

A computational framework for predicting obesity risk based on optimizing and integrating genetic risk score and gene expression profiles.

Recent large-scale genome-wide association studies have identified tens of genetic loci robustly associated with Body Mass Index (BMI). Gene expression profiles were also found to be associated with BMI. However, accurate prediction of obesity risk utilizing genetic data remains challenging. In a cohort of 75 individuals, we integrated 27 BMI-associated SNPs and obesity-associated gene expression profiles. Genetic risk score was computed by adding BMI-increasing alleles. The genetic risk score was significantly correlated with BMI when an optimization algorithm was used that excluded some SNPs. Linear regression and support vector machine models were built to predict obesity risk using gene expression profiles and the genetic risk score. An adjusted R2 of 0.556 and accuracy of 76% was achieved for the linear regression and support vector machine models, respectively. In this paper, we report a new mathematical method to predict obesity genetic risk. We constructed obesity prediction models based on genetic information for a small cohort. Our computational framework serves as an example for using genetic information to predict obesity risk for specific cohorts.

Relationship between fat mass and obesity-associated gene expression and type 2 diabetes mellitus severity.

This study sought to investigate any correlation between fat mass and obesity-associated gene (FTO) expression and the severity of type 2 diabetes mellitus (T2DM). In total 110 patients newly diagnosed with T2DM in the outpatient department of Yantai Yuhuangding Hospital between September 2016 and March 2017 were selected as study subjects and were divided into severe (58 cases) and mild groups (52 cases) according to T2DM severity. Patients in the severe group were followed up for 12 weeks. An additional 60 healthy individuals were selected to serve as the normal control group. Fasting plasma glucose (FPG), fasting insulin (FINs), fasting C-peptide (FCP), glycosylated hemoglobin (HbA1c) and homeostasis model assessment of insulin resistance (HOMA-IR) were examined for every patient in the study. Real-time polymerase chain reaction (RT-PCR) was used to detect FTO messenger ribonucleic acid (mRNA) expression levels in patient peripheral blood lymphocytes. Western blotting was used to detect serum FTO protein expression levels, upon which the correlation between FTO protein levels and all other indices were analyzed. Compared with the normal control group, both T2DM groups showed significantly increased waist circumferences, hip circumferences, body mass indexes (BMIs), blood glucose indexes (FPG, FCP, HbA1c, FINs, HOMA-IR) and FTO mRNA/protein levels (p<0.05). Additionally, the increases presented by the severe T2DM group were significantly greater than those presented by the mild T2DM group (p<0.05). After 12 weeks of treatment, the severe T2DM group showed decreased BMI, blood glucose index and FTO protein expression (p<0.05). FTO protein expression in T2DM patients was higher than in healthy controls, with severe patients showing greater expression levels than mild group patients. FTO expression was positively correlated with BMI, waist circumference, chest circumference, FPG, FCP, HbA1c, FINs and HOMA-IR. Therefore, FTO expression can serve as a marker for the clinical diagnosis and treatment of T2DM.

Significant obesity-associated gene expression changes occur in the stomach but not intestines in obese mice.

The gastrointestinal (GI) tract can have significant impact on the regulation of the whole‐body metabolism and may contribute to the development of obesity and diabetes. To systemically elucidate the role of the GI tract in obesity, we performed a transcriptomic analysis in different parts of the GI tract of two obese mouse models: ob/ob and high‐fat diet (HFD) fed mice. Compared to their lean controls, significant changes in the gene expression were observed in both obese mouse groups in the stomach (ob/ob: 959; HFD: 542). In addition, these changes were quantitatively much higher than in the intestine. Despite the difference in genetic background, the two mouse models shared 296 similar gene expression changes in the stomach. Among those genes, some had known associations to obesity, diabetes, and insulin resistance. In addition, the gene expression profiles strongly suggested an increased gastric acid secretion in both obese mouse models, probably through an activation of the gastrin pathway. In conclusion, our data reveal a previously unknown dominant connection between the stomach and obesity in murine models extensively used in research.

Birth weight is associated with placental fat mass- and obesity-associated gene expression and promoter methylation in a Chinese population

Objective: To explore the relationship between birth weight and fat mass- and obesity-associated (FTO) gene expression and promoter methylation status in the Chinese population.Methods: Seventy-five neonates and their mothers were recruited from Yuying Children’s Hospital of Wenzhou Medical University. Subjects were divided into three groups by birth weight: low (<3500 g, n = 20), medium (3500–3999 g, n = 30) and high (≥4000 g, n = 25). Placental FTO transcript levels and promoter methylation were determined by quantitative PCR and Sequenom MassARRAY®.Results: Placental FTO mRNA expression was significantly increased in the high- and medium-weight groups compared to the low-weight group (p = 0.023). Methylation rates of CpG11 sites were significantly decreased in high-birth weight newborns (p = 0.018). Multiple linear regressions showed placental FTO mRNA, maternal pre-pregnancy body mass index (BMI) and CpG11 methylation rate were independently associated with increased fetal birth weight. Additionally, FTO mRNA expression was negatively associated with CpG6.7.8.9 methylation in mothers that underwent C-section.Conclusions: High placental FTO expression is associated with increased birth weight in Chinese neonates, and FTO promoter methylation level at a specific CpG site is negatively associated with birth weight. Further work is needed to determine the functionality of this CpG site in placentas.

730 THE ATORVASTATIN TARGET SCD1 IDENTIFIED WITHIN THE GENE EXPRESSION SIGNATURE OF HIGH BMI PROSTATE CANCER PATIENTS

You have accessJournal of UrologyProstate Cancer: Basic Research1 Apr 2011730 THE ATORVASTATIN TARGET SCD1 IDENTIFIED WITHIN THE GENE EXPRESSION SIGNATURE OF HIGH BMI PROSTATE CANCER PATIENTS Patrick Parker, Shashwat Sharad, Anjali Srivastava, Suma Ravulapalli, Yongmei Chen, Hua Li, Gyorgy Petrovics, and Albert Dobi Patrick ParkerPatrick Parker Washington, DC More articles by this author , Shashwat SharadShashwat Sharad Rockville, MD More articles by this author , Anjali SrivastavaAnjali Srivastava Rockville, MD More articles by this author , Suma RavulapalliSuma Ravulapalli Rockville, MD More articles by this author , Yongmei ChenYongmei Chen Rockville, MD More articles by this author , Hua LiHua Li Rockville, MD More articles by this author , Gyorgy PetrovicsGyorgy Petrovics Rockville, MD More articles by this author , and Albert DobiAlbert Dobi Rockville, MD More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2011.02.1699AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Obesity is one of the largest medical challenges in the USA. Recent studies highlighted the association of obesity with prostate cancer aggressiveness suggesting that obesity-associated altered metabolic conditions may be linked to prostate cancer progression. However, obesity-associated gene expression alterations need to be better understood in prostate cancer. The objective of this study was to evaluate elevated BMI-associated prostate cancer gene expression signatures. METHODS Prostate cancer cells and matching non-adjacent normal epithelial cells were selected by laser capture microdissection from frozen radical prostatectomy specimens of patients with normal- and high BMI. Gene expression analyses were performed by using HG-U133A Affymetrix microarrays. Both Robust Multi-array Analysis and single-probe analysis approaches were employed for data analysis to assure enrichment of significant gene expression alterations. Tumor-over-normal gene expression ratios were calculated and data were further analyzed by applying a three-fold cutoff. To pinpoint central regulatory nodes of gene expression alterations knowledge-based pathway analysis, gene ontology and comparative meta-analysis of obesity related independent datasets were performed. RESULTS Bioinformatic analyses revealed associations of high BMI with cholesterol and lipid metabolism associated genes within fatty acid synthesis and oxidation-reduction pathways. The identified high BMI-associated genes were tightly connected to genes involved in lipid metabolism, cholesterol homeostasis, and tumorigenesis. The analysis highlighted the association of stearoyl-CoA desaturase (SCD1) with elevated BMI. CONCLUSIONS Our study revealed that SCD1, a known target of atorvastatin, may play a mechanistic role in the recently noted beneficial effects of statin treatment in reducing biochemical recurrence of prostate cancer. © 2011 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 185Issue 4SApril 2011Page: e293 Advertisement Copyright & Permissions© 2011 by American Urological Association Education and Research, Inc.MetricsAuthor Information Patrick Parker Washington, DC More articles by this author Shashwat Sharad Rockville, MD More articles by this author Anjali Srivastava Rockville, MD More articles by this author Suma Ravulapalli Rockville, MD More articles by this author Yongmei Chen Rockville, MD More articles by this author Hua Li Rockville, MD More articles by this author Gyorgy Petrovics Rockville, MD More articles by this author Albert Dobi Rockville, MD More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...