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Genomics and Obesity

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https://www.readbyqxmd.com/read/29453460/development-and-initial-characterization-of-a-novel-ghrelin-receptor-crispr-cas9-knockout-wistar-rat-model
#1
L J Zallar, B J Tunstall, C T Richie, Y J Zhang, Z B You, E L Gardner, M Heilig, J Pickel, G F Koob, L F Vendruscolo, B K Harvey, L Leggio
BACKGROUND/OBJECTIVES: Ghrelin, a stomach-derived hormone implicated in numerous behaviors including feeding, reward, stress, and addictive behaviors, acts by binding to the growth hormone secretagogue receptor (GHSR). Here, we present the development, verification, and initial characterization of a novel GHSR knockout (KO) Wistar rat model created with CRISPR genome editing. METHODS: Using CRISPR/Cas9, we developed a GHSR KO in a Wistar background. Loss of GHSR mRNA expression was histologically verified using RNAscope in wild-type (WT; n = 2) and KO (n = 2) rats...
January 30, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29449090/clinical-and-molecular-characteristics-and-burden-of-kidney-cancer-among-hispanics-and-native-americans-steps-toward-precision-medicine
#2
Ken Batai, Andrew Bergersen, Elinora Price, Kieran Hynes, Nathan A Ellis, Benjamin R Lee
Cancer disparities in Native Americans (NAs) and Hispanic Americans (HAs) vary significantly in terms of cancer incidence and mortality rates across geographic regions. This review reports that kidney and renal pelvis cancers are unevenly affecting HAs and NAs compared to European Americans of non-Hispanic origin, and that currently there is significant need for improved data and reporting to be able to advance toward genomic-based precision medicine for the assessment of such cancers in these medically underserved populations...
February 12, 2018: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/29444804/partitioning-the-pleiotropy-between-coronary-artery-disease-and-body-mass-index-reveals-the-importance-of-low-frequency-variants-and-central-nervous-system-specific-functional-elements
#3
Majid Nikpay, Adam W Turner, Ruth McPherson
BACKGROUND: The objective of this study is to investigate the extent and nature of pleiotropy between coronary artery disease (CAD) and body mass index (BMI). METHODS: We examined the contribution of genome-wide single-nucleotide polymorphisms (minor allele frequency ≥0.01) to co-occurrence of CAD and BMI in a sample of genetically unrelated 8041 subjects (genetic resemblance ≤0.025) of European ancestry using mixed-linear-models. We further partitioned the estimated pleiotropy according to biological features to gain insight into the nature of pleiotropy between CAD and BMI...
February 2018: Circ Genom Precis Med
https://www.readbyqxmd.com/read/29444639/differential-expression-of-mrna-isoforms-in-the-skeletal-muscle-of-pigs-with-distinct-growth-and-fatness-profiles
#4
Tainã Figueiredo Cardoso, Raquel Quintanilla, Anna Castelló, Rayner González-Prendes, Marcel Amills, Ángela Cánovas
BACKGROUND: The identification of genes differentially expressed in the skeletal muscle of pigs displaying distinct growth and fatness profiles might contribute to identify the genetic factors that influence the phenotypic variation of such traits. So far, the majority of porcine transcriptomic studies have investigated differences in gene expression at a global scale rather than at the mRNA isoform level. In the current work, we have investigated the differential expression of mRNA isoforms in the gluteus medius (GM) muscle of 52 Duroc HIGH (increased backfat thickness, intramuscular fat and saturated and monounsaturated fatty acids contents) and LOW pigs (opposite phenotype, with an increased polyunsaturated fatty acids content)...
February 14, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29444131/chromatin-immunoprecipitation-improvements-for-the-processing-of-small-frozen-pieces-of-adipose-tissue
#5
Daniel Castellano-Castillo, Pierre-Damien Denechaud, Isabel Moreno-Indias, Francisco Tinahones, Lluis Fajas, María Isabel Queipo-Ortuño, Fernando Cardona
Chromatin immunoprecipitation (ChIP) has gained importance to identify links between the genome and the proteome. Adipose tissue has emerged as an active tissue, which secretes a wide range of molecules that have been related to metabolic and obesity-related disorders, such as diabetes, cardiovascular failure, metabolic syndrome, or cancer. In turn, epigenetics has raised the importance in discerning the possible relationship between metabolic disorders, lifestyle and environment. However, ChIP application in human adipose tissue is limited by several factors, such as sample size, frozen sample availability, high lipid content and cellular composition of the tissue...
2018: PloS One
https://www.readbyqxmd.com/read/29441128/chromosomal-microarray-analysis-in-the-genetic-evaluation-of-279-patients-with-syndromic-obesity
#6
Carla Sustek D'Angelo, Monica Castro Varela, Claudia Irene Emílio de Castro, Paulo Alberto Otto, Ana Beatriz Alvarez Perez, Charles Marques Lourenço, Chong Ae Kim, Debora Romeo Bertola, Fernando Kok, Luis Garcia-Alonso, Celia Priszkulnik Koiffmann
Background: Syndromic obesity is an umbrella term used to describe cases where obesity occurs with additional phenotypes. It often arises as part of a distinct genetic syndrome with Prader-Willi syndrome being a classical example. These rare forms of obesity provide a unique source for identifying obesity-related genetic changes. Chromosomal microarray analysis (CMA) has allowed the characterization of new genetic forms of syndromic obesity, which are due to copy number variants (CNVs); however, CMA in large cohorts requires more study...
2018: Molecular Cytogenetics
https://www.readbyqxmd.com/read/29437161/associations-of-adult-genetic-risk-scores-for-adiposity-with-childhood-abdominal-liver-and-pericardial-fat-assessed-by-magnetic-resonance-imaging
#7
C Monnereau, S Santos, A van der Lugt, V W V Jaddoe, J F Felix
BACKGROUND: Genome-wide association studies (GWASs) identified single-nucleotide polymorphisms (SNPs) involved in adult fat distribution. Whether these SNPs also affect abdominal and organ-specific fat accumulation in children is unknown. METHODS: In a population-based prospective cohort study among 1995 children (median age: 9.8 years, 95% range 9.4-10.8), we tested the associations of six genetic risk scores based on previously identified SNPs for childhood body mass index (BMI), adult BMI, liver fat, waist-hip ratio, pericardial fat mass, visceral and subcutaneous adipose tissue ratio (VAT/SAT ratio) and four individual SAT- and VAT-associated SNPs for association with SAT (N=1746), VAT (N=1742), VAT/SAT ratio (N=1738), liver fat fraction (N=1950) and pericardial fat mass (N=1803) measured by magnetic resonance imaging...
December 7, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29434210/epigenetic-modulation-of-fgf21-in-the-perinatal-mouse-liver-ameliorates-diet-induced-obesity-in-adulthood
#8
Xunmei Yuan, Kazutaka Tsujimoto, Koshi Hashimoto, Kenichi Kawahori, Nozomi Hanzawa, Miho Hamaguchi, Takami Seki, Makiko Nawa, Tatsuya Ehara, Yohei Kitamura, Izuho Hatada, Morichika Konishi, Nobuyuki Itoh, Yoshimi Nakagawa, Hitoshi Shimano, Takako Takai-Igarashi, Yasutomi Kamei, Yoshihiro Ogawa
The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood...
February 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29433747/clinical-social-and-genetic-factors-associated-with-obesity-at-12-months-of-age
#9
Sahel Hazrati, Wendy S W Wong, Kathi Huddleston, Yvonne Yui, Nancy Gilchrist, Benjamin D Solomon, John Niederhuber, Suchitra K Hourigan
OBJECTIVE: To examine genomic, social, and clinical risk factors of ≥85 weight for length percentile (WFLP) at 12 months. STUDY DESIGN: Children in this study had whole-genome sequencing, and clinical and social data were collected. WFLPs at 12 months of age were grouped as follows: (1) <85th, (2) ≥85th to <95th, (3) ≥95th to <99th, and (4) ≥99th. Whole-genome sequencing data were used to analyze rare and common variants, and association of clinical and social factors was examined...
February 9, 2018: Journal of Pediatrics
https://www.readbyqxmd.com/read/29425059/prader-willi-syndrome-and-angelman-syndrome-visualisation-of-the-molecular-pathways-for-two-chromosomal-disorders
#10
Friederike Ehrhart, Kelly J M Janssen, Susan L Coort, Chris T Evelo, Leopold M G Curfs
OBJECTIVES: Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two syndromes that are caused by the same chromosomal deletion on 15q11.2-q13. Due to methylation patterns, different genes are responsible for the two distinct phenotypes resulting in the disorders. Patients of both disorders exhibit hypotonia in neonatal stage, delay in development and hypopigmentation. Typical features for PWS include hyperphagia, which leads to obesity, the major cause of mortality, and hypogonadism...
February 9, 2018: World Journal of Biological Psychiatry
https://www.readbyqxmd.com/read/29409712/squeezing-flux-out-of-fat
#11
Alba Gonzalez-Franquesa, Mary-Elizabeth Patti
Merging transcriptomics or metabolomics data remains insufficient for metabolic flux estimation. Ramirez et al. integrate a genome-scale metabolic model with extracellular flux data to predict and validate metabolic differences between white and brown adipose tissue. This method allows both metabolic phenotyping and the identification of potential therapeutic targets for obesity.
February 3, 2018: Trends in Endocrinology and Metabolism: TEM
https://www.readbyqxmd.com/read/29400991/lifestyle-genomics-and-the-metabolic-syndrome-a-review-of-genetic-variants-that-influence-response-to-diet-and-exercise-interventions
#12
Peri H Fenwick, Khursheed Jeejeebhoy, Rupinder Dhaliwal, Dawna Royall, Paula Brauer, Angelo Tremblay, Doug Klein, David M Mutch
Metabolic syndrome (MetS) comprises a cluster of risk factors that includes central obesity, dyslipidemia, impaired glucose homeostasis and hypertension. Individuals with MetS have elevated risk of type 2 diabetes and cardiovascular disease; thus placing significant burdens on social and healthcare systems. Lifestyle interventions (comprised of diet, exercise or a combination of both) are routinely recommended as the first line of treatment for MetS. Only a proportion of people respond, and it has been assumed that psychological and social aspects primarily account for these differences...
February 5, 2018: Critical Reviews in Food Science and Nutrition
https://www.readbyqxmd.com/read/29395842/heterogeneity-in-effects-of-genetically-determined-adiposity-on-insulin-resistance-and-type-2-diabetes-the-atherosclerosis-risk-in-communities-study
#13
Tingting Liu, Changwei Li, Luqi Shen, Ye Shen, Weibo Mao, Shengxu Li
BACKGROUND: A recent genome-wide association study has identified 12 genetic variants robustly associated with body fat percentage (BF%) with diverse cardiometabolic consequences. We developed three genetic risk scores (GRSs) according to the associations of the 12 individual variants with type 2 diabetes (T2D) and test the GRSs' associations with insulin resistance and T2D in the Atherosclerosis Risk in Communities Study. METHODS: In 6895 European-American participants, we calculated GRS-I as the number of BF%-increasing alleles from variants associated with increased risk of T2D, GRS-D from variants associated with decreased risk of T2D, and GRS-ALL from all 12 variants...
January 3, 2018: Journal of Diabetes and its Complications
https://www.readbyqxmd.com/read/29391395/genome-wide-analysis-of-self-reported-risk-taking-behaviour-and-cross-disorder-genetic-correlations-in-the-uk-biobank-cohort
#14
Rona J Strawbridge, Joey Ward, Breda Cullen, Elizabeth M Tunbridge, Sarah Hartz, Laura Bierut, Amy Horton, Mark E S Bailey, Nicholas Graham, Amy Ferguson, Donald M Lyall, Daniel Mackay, Laura M Pidgeon, Jonathan Cavanagh, Jill P Pell, Michael O'Donovan, Valentina Escott-Price, Paul J Harrison, Daniel J Smith
Risk-taking behaviour is a key component of several psychiatric disorders and could influence lifestyle choices such as smoking, alcohol use, and diet. As a phenotype, risk-taking behaviour therefore fits within a Research Domain Criteria (RDoC) approach, whereby identifying genetic determinants of this trait has the potential to improve our understanding across different psychiatric disorders. Here we report a genome-wide association study in 116,255 UK Biobank participants who responded yes/no to the question "Would you consider yourself a risk taker?" Risk takers (compared with controls) were more likely to be men, smokers, and have a history of psychiatric disorder...
February 2, 2018: Translational Psychiatry
https://www.readbyqxmd.com/read/29387454/whole-genome-transcriptomic-insights-into-protective-molecular-mechanisms-in-metabolically-healthy-obese-african-americans
#15
Amadou Gaye, Ayo P Doumatey, Sharon K Davis, Charles N Rotimi, Gary H Gibbons
Several clinical guidelines have been proposed to distinguish metabolically healthy obesity (MHO) from other subgroups of obesity but the molecular mechanisms by which MHO individuals remain metabolically healthy despite having a high fat mass are yet to be elucidated. We conducted the first whole blood transcriptomic study designed to identify specific sets of genes that might shed novel insights into the molecular mechanisms that protect or delay the occurrence of obesity-related co-morbidities in MHO. The study included 29 African-American obese individuals, 8 MHO and 21 metabolically abnormal obese (MAO)...
2018: NPJ Genomic Medicine
https://www.readbyqxmd.com/read/29382920/a-systematic-analysis-highlights-multiple-long-non-coding-rnas-associated-with-cardiometabolic-disorders
#16
Mohsen Ghanbari, Marjolein J Peters, Paul S de Vries, Cindy G Boer, Jeroen G J van Rooij, Yu-Chi Lee, Vinod Kumar, André G Uitterlinden, M Arfan Ikram, Cisca Wijmenga, Jose M Ordovas, Caren E Smith, Joyce B J van Meurs, Stefan J Erkeland, Oscar H Franco, Abbas Dehghan
Genome-wide association studies (GWAS) have identified many susceptibility loci for cardiometabolic disorders. Most of the associated variants reside in non-coding regions of the genome including long non-coding RNAs (lncRNAs), which are thought to play critical roles in diverse biological processes. Here, we leveraged data from the available GWAS meta-analyses on lipid and obesity-related traits, blood pressure, type 2 diabetes, and coronary artery disease and identified 179 associated single-nucleotide polymorphisms (SNPs) in 102 lncRNAs (p-value < 2...
January 30, 2018: Journal of Human Genetics
https://www.readbyqxmd.com/read/29382663/long-non-coding-rna-lncshgl-recruits-hnrnpa1-to-suppress-hepatic-gluconeogenesis-and-lipogenesis
#17
Junpei Wang, Weili Yang, Zhenzhen Chen, Ji Chen, Yuhong Meng, Biaoqi Feng, Libo Sun, Lin Dou, Jian Li, Qinghua Cui, Jichun Yang
Mammalian genomes encode a huge number of LncRNAs with unknown functions. This study determined the role and mechanism of a new LncRNA, LncRNA Suppressor of Hepatic Gluconeogenesis and Lipogenesis (LncSHGL), in regulating hepatic glucose/lipid metabolism. In the livers of obese mice and NAFLD patient, the expression levels of mouse LncSHGL and its human homologous LncRNA B4GALT1-AS1 were reduced. Hepatic LncSHGL restoration improved hyperglycemia, insulin resistance and steatosis in obese diabetic mice, whereas hepatic LncSHGL inhibition promoted fasting hyperglycemia and lipid deposition in normal mice...
January 30, 2018: Diabetes
https://www.readbyqxmd.com/read/29381148/trans-ethnic-analysis-of-metabochip-data-identifies-two-new-loci-associated-with-bmi
#18
J Gong, K K Nishimura, L Fernandez-Rhodes, J Haessler, S Bien, M Graff, U Lim, Y Lu, M Gross, M Fornage, S Yoneyama, C R Isasi, P Buzkova, M Daviglus, D-Y Lin, R Tao, R Goodloe, W S Bush, E Farber-Eger, J Boston, H H Dilks, G Ehret, C C Gu, C E Lewis, K-D H Nguyen, R Cooper, M Leppert, M R Irvin, E P Bottinger, L R Wilkens, C A Haiman, L Park, K R Monroe, I Cheng, D O Stram, C S Carlson, R Jackson, L Kuller, D Houston, C Kooperberg, S Buyske, L A Hindorff, D C Crawford, R J F Loos, L Le Marchand, T C Matise, K E North, U Peters
OBJECTIVE: Body mass index (BMI) is commonly used to assess obesity, which is associated with numerous diseases and negative health outcomes. BMI has been shown to be a heritable, polygenic trait, with close to 100 loci previously identified and replicated in multiple populations. We aim to replicate known BMI loci and identify novel associations in a trans-ethnic study population. SUBJECTS: Using eligible participants from the Population Architecture using Genomics and Epidemiology consortium, we conducted a trans-ethnic meta-analysis of 102 514 African Americans, Hispanics, Asian/Native Hawaiian, Native Americans and European Americans...
December 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29377571/transcriptional-regulatory-mechanisms-in-adipose-and-muscle-tissue-associated-with-composite-glucometabolic-phenotypes
#19
Carl D Langefeld, Mary E Comeau, Neeraj K Sharma, Donald W Bowden, Barry I Freedman, Swapan K Das
OBJECTIVE: Tissue-specific gene expression is associated with individual metabolic measures. However, these measures may not reflect the true but latent underlying biological phenotype. This study reports gene expression associations with multidimensional glucometabolic characterizations of obesity, glucose homeostasis, and lipid traits. METHODS: Factor analysis was computed by using orthogonal rotation to construct composite phenotypes (CPs) from 23 traits in 256 African Americans without diabetes...
January 29, 2018: Obesity
https://www.readbyqxmd.com/read/29377524/model-driven-design-of-a-minimal-medium-for-akkermansia-muciniphila-confirms-mucus-adaptation
#20
Kees C H van der Ark, Steven Aalvink, Maria Suarez-Diez, Peter J Schaap, Willem M de Vos, Clara Belzer
The abundance of the human intestinal symbiont Akkermansia muciniphila has found to be inversely correlated with several diseases, including metabolic syndrome and obesity. A. muciniphila is known to use mucin as sole carbon and nitrogen source. To study the physiology and the potential for therapeutic applications of this bacterium, we designed a defined minimal medium. The composition of the medium was based on the genome-scale metabolic model of A. muciniphila and the composition of mucin. Our results indicate that A...
January 26, 2018: Microbial Biotechnology
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