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Genomics and Obesity

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https://www.readbyqxmd.com/read/28819125/inflammation-and-bone-mineral-density-a-mendelian-randomization-study
#1
Jian V Huang, C Mary Schooling
Osteoporosis is a common age-related disorder leading to an increase in osteoporotic fractures and resulting in significant suffering and disability. Inflammation may contribute to osteoporosis, as it does to many other chronic diseases. We examined whether inflammation is etiologically relevant to osteoporosis, assessed from bone mineral density (BMD), as a new potential target of intervention, or whether it is a symptom/biomarker of osteoporosis. We obtained genetic predictors of inflammatory markers from genome-wide association studies and applied them to a large genome wide association study of BMD...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28812581/nfia-co-localizes-with-ppar%C3%AE-and-transcriptionally-controls-the-brown-fat-gene-program
#2
Yuta Hiraike, Hironori Waki, Jing Yu, Masahiro Nakamura, Kana Miyake, Gaku Nagano, Ryo Nakaki, Ken Suzuki, Hirofumi Kobayashi, Shogo Yamamoto, Wei Sun, Tomohisa Aoyama, Yusuke Hirota, Haruya Ohno, Kenji Oki, Masayasu Yoneda, Andrew P White, Yu-Hua Tseng, Aaron M Cypess, Therese J Larsen, Naja Z Jespersen, Camilla Scheele, Shuichi Tsutsumi, Hiroyuki Aburatani, Toshimasa Yamauchi, Takashi Kadowaki
Brown fat dissipates energy as heat and protects against obesity. Here, we identified nuclear factor I-A (NFIA) as a transcriptional regulator of brown fat by a genome-wide open chromatin analysis of murine brown and white fat followed by motif analysis of brown-fat-specific open chromatin regions. NFIA and the master transcriptional regulator of adipogenesis, PPARγ, co-localize at the brown-fat-specific enhancers. Moreover, the binding of NFIA precedes and facilitates the binding of PPARγ, leading to increased chromatin accessibility and active transcription...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28810559/identification-of-key-genes-and-pathways-associated-with-obesity-in-children
#3
Ling Li, Guangyu Wang, Ning Li, Haiyan Yu, Jianping Si, Jiwen Wang
The present study aimed to identify potential key genes and pathways in obese children in order to explore possible molecular mechanisms associated with child obesity. The array dataset GSE29718 was downloaded from the Gene Expression Omnibus database. Subcutaneous adipose tissue samples derived from 7 obese children and 8 lean children were selected for the analysis. Differentially expressed genes (DEGs) in samples from obese children compared with those from lean children were analyzed by the limma package...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28806763/genome-wide-regulation-of-electro-acupuncture-on-the-neural-stat5-loss-induced-obese-mice
#4
Shu-Ping Fu, Hao Hong, Sheng-Feng Lu, Chen-Jun Hu, Hou-Xi Xu, Qian Li, Mei-Ling Yu, Chen Ou, Jian-Zhong Meng, Tian-Lin Wang, Lothar Hennighausen, Bing-Mei Zhu
Acupuncture is reported to be effective in treating obesity related illnesses, but its mechanism is still unclear. To investigate this mechanism we applied electro-acupuncture (EA) in a mouse model of obesity and used RNA-seq to identify molecular consequences. Deletion of the transcription factor STAT5 from neurons (Stat5NKO) led to obesity. Acupuncture, in turn, reduced body weight and the ratio of epididymal white adipose tissue (Epi-WAT) to body weight, and it also decreased plasma concentrations of glucose, triglyceride, and cholesterol...
2017: PloS One
https://www.readbyqxmd.com/read/28804972/mendelian-randomisation-analysis-provides-no-evidence-for-a-relationship-between-adult-height-and-testicular-cancer-risk
#5
M Levy, D Hall, A Sud, P Law, K Litchfield, D Dudakia, T B Haugen, R Karlsson, A Reid, R A Huddart, T Grotmol, F Wiklund, R S Houlston, C Turnbull
Observational studies have suggested anthropometric traits, particularly increased height are associated with an elevated risk of testicular cancer (testicular germ cell tumour). However, there is an inconsistency between study findings, suggesting the possibility of the influence of confounding factors. To examine the association between anthropometric traits and testicular germ cell tumour using an unbiased approach, we performed a Mendelian randomisation study. We used genotype data from genome wide association studies of testicular germ cell tumour totalling 5518 cases and 19,055 controls...
August 13, 2017: Andrology
https://www.readbyqxmd.com/read/28799667/coadministration-of-isomalto-oligosaccharides-augments-metabolic-health-benefits-of-cinnamaldehyde-in-high-fat-diet-fed-mice
#6
Dhirendra Pratap Singh, Pragyanshu Khare, Vandana Bijalwan, Ritesh Kumar Baboota, Jagdeep Singh, Kanthi Kiran Kondepudi, Kanwaljit Chopra, Mahendra Bishnoi
Bacteriostatic properties of a potential anti-obesity agent cinnamaldehyde (CMN) may present untoward effects on the resident gut microbiota. Here, we evaluated whether the combination of Isomalto-oligosaccharides (IMOs) with CMN prevents unwanted effects of CMN on gut microbiota and associated metabolic outcomes in HFD-fed mice. Male Swiss albino mice divided into four groups (n = 10), were fed on normal chow, or HFD (58% fat kcal), HFD + CMN (10 mg kg(-1) ) and HFD + CMN (10 mg kg(-1) ) + IMOs (1 g kg(-1) ) for 12 weeks...
August 11, 2017: BioFactors
https://www.readbyqxmd.com/read/28799494/contribution-of-large-animals-to-translational-research-on-prenatal-programming-of-obesity-and-associated-diseases
#7
Antonio Gonzalez-Bulnes, Pascale Chavatte-Palmer
BACKGROUND: The awareness of factors causing obesity and associated disorders has grown up in the last years from genome to a more complicated concept (developmental programming) in which prenatal and early-postnatal conditions markedly modify the phenotype and homeostasis of the individuals and determine juvenile growth, life-time fitness/obesity and disease risks. Experimentation in human beings is impeded by ethical issues plus inherent high variability and confounding factors (genetics, lifestyle and socioeconomic heterogeneity) and preclinical studies in adequate translational animal models are therefore decisive...
August 11, 2017: Current Pharmaceutical Biotechnology
https://www.readbyqxmd.com/read/28799012/mtdna-genomes-reveal-a-relaxation-of-selective-constraints-in-low-bmi-individuals-in-a-uyghur-population
#8
Hong-Xiang Zheng, Lei Li, Xiao-Yan Jiang, Shi Yan, Zhendong Qin, Xiaofeng Wang, Li Jin
Considerable attention has been focused on the effect of deleterious mutations caused by the recent relaxation of selective constraints on human health, including the prevalence of obesity, which might represent an adaptive response of energy-conserving metabolism under the conditions of modern society. Mitochondrial DNA (mtDNA) encoding 13 core subunits of oxidative phosphorylation plays an important role in metabolism. Therefore, we hypothesized that a relaxation of selection constraints on mtDNA and an increase in the proportion of deleterious mutations have played a role in obesity prevalence...
August 10, 2017: Human Genetics
https://www.readbyqxmd.com/read/28792545/contribution-of-independent-and-pleiotropic-genetic-effects-in-the-metabolic-syndrome-in-a-hypertensive-rat
#9
Man Chun John Ma, Janette M Pettus, Jessica A Jakoubek, Matthew G Traxler, Karen C Clark, Amanda K Mennie, Anne E Kwitek
Hypertension is a major risk factor for cardiovascular disease, Type 2 diabetes, and end organ failure, and is often found concomitant with disorders characteristic of the Metabolic Syndrome (MetS), including obesity, dyslipidemia, and insulin resistance. While the associated features often occur together, the pathway(s) or mechanism(s) linking hypertension in MetS are not well understood. Previous work determined that genetic variation on rat chromosome 17 (RNO17) contributes to several MetS-defining traits (including hypertension, obesity, and dyslipidemia) in the Lyon Hypertensive (LH) rat, a genetically determined MetS model...
2017: PloS One
https://www.readbyqxmd.com/read/28777946/engineered-epidermal-progenitor-cells-can-correct-diet-induced-obesity-and-diabetes
#10
Jiping Yue, Xuewen Gou, Yuanyuan Li, Barton Wicksteed, Xiaoyang Wu
Somatic gene therapy is a promising approach for treating otherwise terminal or debilitating diseases. The human skin is a promising conduit for genetic engineering, as it is the largest and most accessible organ, epidermal autografts and tissue-engineered skin equivalents have been successfully deployed in clinical applications, and skin epidermal stem/progenitor cells for generating such grafts are easy to obtain and expand in vitro. Here, we develop skin grafts from mouse and human epidermal progenitors that were engineered by CRISPR-mediated genome editing to controllably release GLP-1 (glucagon-like peptide 1), a critical incretin that regulates blood glucose homeostasis...
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28774683/dietary-linoleic-acid-interacts-with-fads1-genetic-variability-to-modulate-hdl-cholesterol-and-obesity-related-traits
#11
Julie Dumont, Louisa Goumidi, Benjamin Grenier-Boley, Dominique Cottel, Nadine Marécaux, Michèle Montaye, Aline Wagner, Dominique Arveiler, Chantal Simon, Jean Ferrières, Jean-Bernard Ruidavets, Philippe Amouyel, Jean Dallongeville, Aline Meirhaeghe
BACKGROUND & AIMS: Blood levels of polyunsaturated fatty acids (PUFAs) are under control of endogenous synthesis via Δ5- and Δ6-desaturases, encoded by the FADS1 and FADS2 genes, respectively and of diet. Genome-wide associations studies (GWAS) reported associations between polymorphisms in FADS1-FADS2 and variations in plasma concentrations of PUFAs, HDL- and LDL-cholesterol and triglycerides. However, it is not established whether dietary PUFAs intake modulates these associations...
July 20, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28764799/metabolomics-study-of-the-therapeutic-mechanism-of-schisandra-chinensis-lignans-in-diet-induced-hyperlipidemia-mice
#12
Jing-Hui Sun, Xu Liu, Li-Xin Cong, He Li, Cheng-Yi Zhang, Jian-Guang Chen, Chun-Mei Wang
BACKGROUND: Schisandra, a globally distributed plant, has been widely applied for the treatment of diseases such as hyperlipidemia, fatty liver and obesity in China. In the present work, a rapid resolution liquid chromatography coupled with quadruple-time-of-flight mass spectrometry (RRLC-Q-TOF-MS)-based metabolomics was conducted to investigate the intervention effect of Schisandra chinensis lignans (SCL) on hyperlipidemia mice induced by high-fat diet (HFD). METHODS: Hyperlipidemia mice were orally administered with SCL (100 mg/kg) once a day for 4 weeks...
August 1, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28763444/childhood-adiposity-and-risk-of-type-1-diabetes-a-mendelian-randomization-study
#13
J C Censin, Christoph Nowak, Nicholas Cooper, Peter Bergsten, John A Todd, Tove Fall
BACKGROUND: The incidence of type 1 diabetes (T1D) is increasing globally. One hypothesis is that increasing childhood obesity rates may explain part of this increase, but, as T1D is rare, intervention studies are challenging to perform. The aim of this study was to assess this hypothesis with a Mendelian randomization approach that uses genetic variants as instrumental variables to test for causal associations. METHODS AND FINDINGS: We created a genetic instrument of 23 single nucleotide polymorphisms (SNPs) associated with childhood adiposity in children aged 2-10 years...
August 2017: PLoS Medicine
https://www.readbyqxmd.com/read/28753864/predicting-prostate-cancer-progression-as-a-function-of-ets-related-gene-status-race-and-obesity-in-a-longitudinal-patient-cohort
#14
Jennifer Cullen, Denise Young, Yongmei Chen, Michael Degon, James Farrell, Jason Sedarsky, Wagner Baptiste, Philip Rosen, Vladimir Tolstikov, Michael Kiebish, Jacob Kagan, Sudhir Srivastava, Huai-Ching Kuo, Joel T Moncur, Inger L Rosner, Niven Narain, Viatcheslav Akmaev, Gyorgy Petrovics, Albert Dobi, David G McLeod, Shiv Srivastava, Isabell A Sesterhenn
BACKGROUND: ETS-related gene (ERG) oncogenic activation is the most common genomic alteration in prostate cancer (CaP) although it occurs less frequently in African American (AA) versus Caucasian (CA) patients, and the potential role of ERG as a prognostic marker has not been confirmed. OBJECTIVE: This study was conducted to confirm strong racial variation in the prevalence of ERG oncoprotein expression and to examine ERG oncoprotein expression, race, and body mass index as independent and joint predictors of CaP biochemical recurrence (BCR) following radical prostatectomy (RP)...
March 11, 2017: European Urology Focus
https://www.readbyqxmd.com/read/28752194/from-engineering-to-editing-the-rat-genome
#15
Stephen Meek, Tomoji Mashimo, Tom Burdon
Since its domestication over 100 years ago, the laboratory rat has been the preferred experimental animal in many areas of biomedical research (Lindsey and Baker The laboratory rat. Academic, New York, pp 1-52, 2006). Its physiology, size, genetics, reproductive cycle, cognitive and behavioural characteristics have made it a particularly useful animal model for studying many human disorders and diseases. Indeed, through selective breeding programmes numerous strains have been derived that are now the mainstay of research on hypertension, obesity and neurobiology (Okamoto and Aoki Jpn Circ J 27:282-293, 1963; Zucker and Zucker J Hered 52(6):275-278, 1961)...
July 27, 2017: Mammalian Genome: Official Journal of the International Mammalian Genome Society
https://www.readbyqxmd.com/read/28748911/a-novel-and-quick-pcr-based-method-to-genotype-mice-with-a-leptin-receptor-mutation-db-db-mice
#16
Bao-Yu Peng, Qiang Wang, Yan-Hong Luo, Jian-Feng He, Tao Tan, Hua Zhu
db/db mice is one of most widely used animal models in studying the cellular and molecular mechanisms of metabolic disorders, such as diabetes, hyperlipidemia, and obesity. The mice carry spontaneous point mutations in the gene encoding the leptin receptor, leading to leptin receptor inactivation. Since homozygous db/db mice are sterile, the maintenance of db/db mice requires breeding between heterozygous pairs, which makes genotyping essential for the identification of offspring. The aim of this study was to develop a quick and highly repeatable method for genotyping db/db mice, which comprised only three simple steps: Genomic DNA is extracted from either tail tips or ear notches via alkaline lysis (∼20 min); Samples are then subjected to tetra-primer amplification refractory mutation system-polymerase chain reaction (ARMS-PCR) using specially designed and validated primer sets (∼1...
July 27, 2017: Acta Pharmacologica Sinica
https://www.readbyqxmd.com/read/28746203/the-fto-rs9939609-polymorphism-is-associated-with-short-leukocyte-telomere-length-in-nonobese-individuals
#17
Ji Hee Yu, Inkyung Baik, Hyun Joo Cho, Ji A Seo, Sin Gon Kim, Kyung Mook Choi, Sei Hyun Baik, Dong Seop Choi, Chol Shin, Nan Hee Kim
The fat mass and obesity-associated (FTO) rs9939609 polymorphism have been associated with the increased metabolic risk and mortality, irrespective of obesity. The mechanism underlying this association is not known. We aimed to evaluate whether the FTO rs9939609 risk variant is independently associated with metabolic risk factors and/or leukocyte telomere length (LTL). We further aimed to investigate whether this relationship is modified by obesity status.A total of 2133 participants were recruited from the Korean Genome and Epidemiology Study...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28745372/systems-level-organization-of-non-alcoholic-fatty-liver-disease-progression-network
#18
K Shubham, L Vinay, P K Vinod
Non-Alcoholic Fatty Liver Disease (NAFLD) is a complex spectrum of diseases ranging from simple steatosis to Non-Alcoholic Steatohepatitis (NASH) with fibrosis, which can progress to cirrhosis and hepatocellular carcinoma. The pathogenesis of NAFLD is complex, involving crosstalk between multiple organs, cell-types, and environmental and genetic factors. Dysfunction of the adipose tissue plays a central role in NAFLD progression. Here, we analysed transcriptomics data obtained from the Visceral Adipose Tissue (VAT) of NAFLD patients to understand how the VAT metabolism is altered at the genome scale and co-regulated with other cellular processes during the progression from obesity to NASH with fibrosis...
July 26, 2017: Molecular BioSystems
https://www.readbyqxmd.com/read/28738459/-gene-gene-interaction-on-central-obesity-in-school-aged-children-in-china
#19
L W Fu, M X Zhang, L J Wu, L W Gao, J Mi
Objective: To investigate possible effect of 6 obesity-associated SNPs in contribution to central obesity and examine whether there is an interaction in the 6 SNPs in the cause of central obesity in school-aged children in China. Methods: A total of 3 502 school-aged children who were included in Beijing Child and Adolescent Metabolic Syndrome (BCAMS) Study were selected, and based on the age and sex specific waist circumference (WC) standards in the BCAMS study, 1 196 central obese cases and 2 306 controls were identified...
July 10, 2017: Zhonghua Liu Xing Bing Xue za Zhi, Zhonghua Liuxingbingxue Zazhi
https://www.readbyqxmd.com/read/28735903/genetics-of-non-syndromic-childhood-obesity-and-the-use-of-high-throughput-dna-sequencing-technologies
#20
REVIEW
Ana Carolina Proença da Fonseca, Claudio Mastronardi, Angad Johar, Mauricio Arcos-Burgos, Gilberto Paz-Filho
BACKGROUND: Childhood obesity is a serious public health problem associated with the development of several chronic diseases, such as type 2 diabetes mellitus, dyslipidemia, and hypertension. The elevated prevalence of obesity is mostly due to inadequate diet and lifestyle, but it is also influenced by genetic factors. OBJECTIVES: To review recent advances in the field of the genetics of obesity. We summarize the list of genes associated with the rare non-syndromic forms of obesity, and explain their function...
June 16, 2017: Journal of Diabetes and its Complications
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