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Genomics and Obesity

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https://www.readbyqxmd.com/read/29221131/hoxa5-increases-mitochondrial-apoptosis-by-inhibiting-akt-mtorc1-s6k1-pathway-in-mice-white-adipocytes
#1
Fei Feng, Qian Ren, Song Wu, Muhammad Saeed, Chao Sun
Homeobox A5(Hoxa5), a member of the Hox family, plays a important role in the regulation of proliferation and apoptosis in cancer cells. The dysregulation of the adipocyte apoptosis in vivo leads to obesity and metabolic disorders. However, the effects of Hoxa5 on adipocyte apoptosis are still unknown. In this study, palmitic acid (PA) significantly increased the mRNA level of Hoxa5 and triggered white adipocyte apoptosis in vivo and in vitro. Further analysis revealed that Hoxa5 enhanced the early and late apoptotic cells and fragmentation of genomic DNA in adipocytes from inguinal white adipose tissue (iWAT) of mice...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29220752/genomic-characterization-of-the-porcine-crtc3-and-the-effects-of-a-non-synonymous-mutation-p-v515f-on-lean-meat-production-and-belly-fat
#2
S H Lee, M H Hur, E A Lee, K C Hong, J M Kim
cAMP-responsive element-binding protein (CREB)-regulated transcriptional coactivator 3 (CRTC3) is well known to be related to obesity in humans and mice. However, the effects of CRTC3 have not been studied in pigs. Here, we characterized the structure of the porcine CRTC3 gene and identified single nucleotide polymorphisms (SNPs) in its coding region. Moreover, mRNA expression profiles of CRTC3 in muscle and fat tissues were examined. Of the 40 identified SNPs, the p.V515F mutation, located on exon 16, was genotyped in 368 Yorkshire pigs...
November 20, 2017: Meat Science
https://www.readbyqxmd.com/read/29220483/prenatal-exposure-to-bisphenol-a-disrupts-naturally-occurring-bimodal-dna-methylation-at-proximal-promoter-of-fggy-an-obesity-relevant-gene-encoding-a-carbohydrate-kinase-in-gonadal-white-adipose-tissues-of-cd-1-mice
#3
Julia A Taylor, Keiko Shioda, Shino Mitsunaga, Shiomi Yawata, Brittany M Angle, Susan C Nagel, Frederick S Vom Saal, Toshi Shioda
Exposure of mammalian fetuses to endocrine disruptors can increase the risk of adult-onset diseases. For example, we previously showed that exposure of mouse fetuses to bisphenol A (BPA) caused adult-onset obesity. To obtain insights into roles of epigenetic changes in the delayed toxic effects of endocrine disruption, we determined effects of fetal mouse exposure to BPA on genome-wide DNA methylation and mRNA expression in gonadal white adipose tissues by deep sequencing (MBD-seq and RNA-seq), bisulfite pyrosequencing, and real-time qPCR...
December 6, 2017: Endocrinology
https://www.readbyqxmd.com/read/29217450/cadm2-regulates-body-weight-and-energy-homeostasis-in-mice
#4
Xin Yan, Zhen Wang, Vanessa Schmidt, Anton Gauert, Thomas E Willnow, Matthias Heinig, Matthew N Poy
OBJECTIVE: Obesity is strongly linked to genes regulating neuronal signaling and function, implicating the central nervous system in the maintenance of body weight and energy metabolism. Genome-wide association studies identified significant associations between body mass index (BMI) and multiple loci near Cell adhesion molecule2 (CADM2), which encodes a mediator of synaptic signaling enriched in the brain. Here we sought to further understand the role of Cadm2 in the pathogenesis of hyperglycemia and weight gain...
November 22, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29212175/the-role-of-established-east-asian-obesity-related-loci-on-pediatric-leptin-levels-highlights-a-neuronal-influence-on-body-weight-regulation-in-chinese-children-and-adolescents-the-bcams-study
#5
Junling Fu, Ge Li, Lujiao Li, Jinhua Yin, Hong Cheng, Lanwen Han, Qian Zhang, Naishi Li, Xinhua Xiao, Struan F A Grant, Mingyao Li, Shan Gao, Jie Mi, Ming Li
Genome-wide association studies have identified multiple variants associated with adult obesity, mostly in European-ancestry populations. We aimed to systematically assess the contribution of key loci, which had been previously shown to be associated in East Asian adults, to childhood obesity, related adipokine profiles and metabolic traits in a Chinese pediatric population. Twelve single-nucleotide polymorphisms (SNPs) plus metabolic profiles and levels of five adipokines (leptin, adiponectin, resistin, fibroblast growth factor 21 and retinol binding protein 4) were evaluated in 3,506 Chinese children and adolescents aged 6-18...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211707/obesity-and-obesogenic-growth-are-both-highly-heritable-and-modified-by-diet-in-a-nonhuman-primate-model-the-african-green-monkey-chlorocebus-aethiops-sabaeus
#6
C A Schmitt, S K Service, A J Jasinska, T D Dyer, M J Jorgensen, R M Cantor, G M Weinstock, J Blangero, J R Kaplan, N B Freimer
OBJECTIVE: In humans, the ontogeny of obesity throughout the life course and the genetics underlying it has been historically difficult to study. We compared, in a non-human primate model, the lifelong growth trajectories of obese and non-obese adults, to assess the heritability of and map potential genomic regions implicated in growth and obesity. STUDY POPULATION: A total of 905 African green monkeys, or vervets (Chlorocebus aethiops sabaeus) (472 females, 433 males) from a pedigreed captive colony...
December 6, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29193816/genetic-fine-mapping-and-identification-of-candidate-genes-and-variants-for-adiposity-traits-in-outbred-rats
#7
Gregory R Keele, Jeremy W Prokop, Hong He, Katie Holl, John Littrell, Aaron Deal, Sanja Francic, Leilei Cui, Daniel M Gatti, Karl W Broman, Michael Tschannen, Shirng-Wern Tsaih, Maie Zagloul, Yunjung Kim, Brittany Baur, Joseph Fox, Melanie Robinson, Shawn Levy, Michael J Flister, Richard Mott, William Valdar, Leah C Solberg Woods
OBJECTIVE: Obesity is a major risk factor for multiple diseases and is in part heritable, yet the majority of causative genetic variants that drive excessive adiposity remain unknown. Here, outbred heterogeneous stock (HS) rats were used in controlled environmental conditions to fine-map novel genetic modifiers of adiposity. METHODS: Body weight and visceral fat pad weights were measured in male HS rats that were also genotyped genome-wide. Quantitative trait loci (QTL) were identified by genome-wide association of imputed single-nucleotide polymorphism (SNP) genotypes using a linear mixed effect model that accounts for unequal relatedness between the HS rats...
November 28, 2017: Obesity
https://www.readbyqxmd.com/read/29189723/long-non-coding-rnas-in-metabolic-organs-and-energy-homeostasis
#8
REVIEW
Maude Giroud, Marcel Scheideler
Single cell organisms can surprisingly exceed the number of human protein-coding genes, which are thus not at the origin of the complexity of an organism. In contrast, the relative amount of non-protein-coding sequences increases consistently with organismal complexity. Moreover, the mammalian transcriptome predominantly comprises non-(protein)-coding RNAs (ncRNA), of which the long ncRNAs (lncRNAs) constitute the most abundant part. lncRNAs are highly species- and tissue-specific with very versatile modes of action in accordance with their binding to a large spectrum of molecules and their diverse localization...
November 30, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29188820/identification-of-novel-alleles-associated-with-insulin-resistance-in-childhood-obesity-using-pooled-dna-genome-wide-association-study-approach
#9
P Kotnik, E Knapič, J Kokošar, J Kovač, R Jerala, T Battelino, S Horvat
BACKGROUND: Recently, we witnessed great progress in the discovery of genetic variants associated with obesity and T2D, especially in adults. Much less is known regarding genetic variants associated with insulin resistance (IR). We hypothesized that novel IR genes could be efficiently detected in a population of obese children and adolescents who may not exhibit comorbidities and other confounding factors. OBJECTIVES: This study aimed to determine if a genome wide association study (GWAS), using a DNA pooling approach, could identify novel genes associated with IR...
November 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29188632/-advance-in-clinical-application-of-non-invasive-prenatal-screening-using-cell-free-fetal-dna
#10
Jilin Hu, Baosheng Zhu
Non-invasive prenatal screening using cell-free fetal DNA (NIPS) has been integrated into the prenatal health care only in a short span of five years, and the guidelines provided by professional bodies have been continuously updated. The American College of Medical Genetics and Genomics has made a statement on NIPS in July, 2016, suggesting that the NIPS can replace conventional screening for Patau, Edwards and Down syndromes in a continuum of gestational age and for any maternal age, except those who are significantly obese...
December 10, 2017: Zhonghua Yi Xue Yi Chuan Xue za Zhi, Zhonghua Yixue Yichuanxue Zazhi, Chinese Journal of Medical Genetics
https://www.readbyqxmd.com/read/29187737/the-role-of-cnvs-in-the-etiology-of-rare-autosomal-recessive-disorders-the-example-of-trappc9-associated-intellectual-disability
#11
Jérémie Mortreux, Tiffany Busa, Dominique P Germain, Gwenaël Nadeau, Jacques Puechberty, Christine Coubes, Vincent Gatinois, Pierre Cacciagli, Yannis Duffourd, Jean-Marc Pinard, Hélène Tevissen, Laurent Villard, Damien Sanlaville, Nicole Philip, Chantal Missirian
INTRODUCTION: A large number of genes involved in autosomal recessive forms of intellectual disability (ID) were identified over the past few years through whole-exome sequencing (WES) or whole-genome sequencing in consanguineous families. Disease-associated variants in TRAPPC9 were reported in eight multiplex consanguineous sibships from different ethnic backgrounds, and led to the delineation of the phenotype. Affected patients have microcephaly, obesity, normal motor development, severe ID, and language impairment and brain anomalies...
November 29, 2017: European Journal of Human Genetics: EJHG
https://www.readbyqxmd.com/read/29186889/a-strategy-for-identifying-quantitative-trait-genes-using-gene-expression-analysis-and-causal-analysis
#12
REVIEW
Akira Ishikawa
Large numbers of quantitative trait loci (QTL) affecting complex diseases and other quantitative traits have been reported in humans and model animals. However, the genetic architecture of these traits remains elusive due to the difficulty in identifying causal quantitative trait genes (QTGs) for common QTL with relatively small phenotypic effects. A traditional strategy based on techniques such as positional cloning does not always enable identification of a single candidate gene for a QTL of interest because it is difficult to narrow down a target genomic interval of the QTL to a very small interval harboring only one gene...
November 27, 2017: Genes
https://www.readbyqxmd.com/read/29186452/gender-and-cardiovascular-disease-are-sex-biased-mirna-networks-a-driving-force-behind-heart-failure-with-preserved-ejection-fraction-in-women
#13
Barend W Florijn, Roel Bijkerk, Eric van der Veer, Anton Jan van Zonneveld
CVD is the primary cause of death among men and women worldwide. Nevertheless, our comprehension of how CVD progresses in women and elicits clinical outcomes is lacking, leading CVD to be under-diagnosed and under-treated in women. A clear example of this differential presentation of CVD pathophysiologies in females is the strikingly higher prevalence of heart failure with preserved ejection fraction (HFpEF). Women with a history of preeclampsia, or those that present co-morbidities such as obesity, hypertension and diabetes mellitus are at increased risk to develop HFpEF...
November 24, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/29183623/role-of-angiopoietin-like-3-angptl3-in-regulating-plasma-level-of-low-density-lipoprotein-cholesterol
#14
Yu-Xin Xu, Valeska Redon, Haojie Yu, William Querbes, James Pirruccello, Abigail Liebow, Amy Deik, Kevin Trindade, Xiao Wang, Kiran Musunuru, Clary B Clish, Chad Cowan, Kevin Fizgerald, Daniel Rader, Sekar Kathiresan
BACKGROUND AND AIMS: Angiopoietin-like 3 (ANGPTL3) has emerged as a key regulator of lipoprotein metabolism in humans. Homozygous loss of ANGPTL3 function causes familial combined hypolipidemia characterized by low plasma levels of triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). While known effects of ANGPTL3 in inhibiting lipoprotein lipase and endothelial lipase contribute to the low TG and HDL-C, respectively, the basis of low LDL-C remains unclear...
September 21, 2017: Atherosclerosis
https://www.readbyqxmd.com/read/29181734/pleiotropy-of-cardiometabolic-syndrome-with-obesity-related-anthropometric-traits-determined-using-empirically-derived-kinships-from-the-busselton-health-study
#15
Gemma Cadby, Phillip E Melton, Nina S McCarthy, Marcio Almeida, Sarah Williams-Blangero, Joanne E Curran, John L VandeBerg, Jennie Hui, John Beilby, A W Musk, Alan L James, Joseph Hung, John Blangero, Eric K Moses
Over two billion adults are overweight or obese and therefore at an increased risk of cardiometabolic syndrome (CMS). Obesity-related anthropometric traits genetically correlated with CMS may provide insight into CMS aetiology. The aim of this study was to utilise an empirically derived genetic relatedness matrix to calculate heritabilities and genetic correlations between CMS and anthropometric traits to determine whether they share genetic risk factors (pleiotropy). We used genome-wide single nucleotide polymorphism (SNP) data on 4671 Busselton Health Study participants...
November 27, 2017: Human Genetics
https://www.readbyqxmd.com/read/29180724/novel-common-variants-associated-with-obesity-and-type-2-diabetes-detected-using-a-cfdr-method
#16
Qiang Zhang, Ke-Hao Wu, Jing-Yang He, Yong Zeng, Jonathan Greenbaum, Xin Xia, Hui-Min Liu, Wan-Qiang Lv, Xu Lin, Wei-Dong Zhang, Yuan-Lin Xi, Xue-Zhong Shi, Chang-Qing Sun, Hong-Wen Deng
Genome-wide association studies (GWASs) have been performed extensively in diverse populations to identify single nucleotide polymorphisms (SNPs) associated with complex diseases or traits. However, to date, the SNPs identified fail to explain a large proportion of the variance of the traits/diseases. GWASs on type 2 diabetes (T2D) and obesity are generally focused on individual traits independently, and genetic intercommunity (common genetic contributions or the product of over correlated phenotypic world) between them are largely unknown, despite extensive data showing that these two phenotypes share both genetic and environmental risk factors...
November 27, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29179200/stress-kinase-regulation-of-task-1-and-task-3
#17
Susanne Rinné, Aytug K Kiper, Constanze Schmidt, Beatriz Ortiz-Bonnin, Simone Zwiener, Guiscard Seebohm, Niels Decher
BACKGROUND/AIMS: TASK channels belong to the two-pore-domain potassium (K2P) channel family. TASK-1 is discussed to contribute to chronic atrial fibrillation (AFib) and has been together with uncoupling protein 1 found as a marker protein of brown adipose tissue (BAT) fat. In addition, TASK-1 was linked in a genome-wide association study to an increased body mass index. A recent study showed that TASK-1 inhibition is causing obesity in mice by a BAT whitening and that these effects are linked to the mineralocorticoid receptor pathway, albeit the mechanism remained elusive...
November 27, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29177584/sirtuin-6-a-possible-therapeutic-target-for-type-2-diabetes
#18
REVIEW
Eun Ju Bae
Sirtuin 6 (SIRT6), one of the seven members of mammalian sirtuin family, localizes in the nucleus and primarily regulates chromatin signaling and genomic integrity. Recent studies established the critical role of SIRT6 in the pathophysiology of metabolic disease, as well as its roles in longevity and cancer. These roles that were determined by genetic studies include promoting pancreatic insulin secretion, inhibiting hepatic gluconeogenesis and triglyceride synthesis, and suppressing adiposity, suggesting that SIRT6 activators are promising molecules for treating obesity and diabetes...
November 25, 2017: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/29172946/postprandial-gut-microbiota-driven-choline-metabolism-links-dietary-cues-to-adipose-tissue-dysfunction
#19
Rebecca C Schugar, Belinda Willard, Zeneng Wang, J Mark Brown
The human body is an integrated circuit between microbial symbionts and our Homo sapien genome, which communicate bi-directionally to maintain homeostasis within the human meta-organism. There is now strong evidence that microbes resident in the human intestine can directly contribute to the pathogenesis of obesity and associated cardiometabolic disorders. In fact, gut microbes represent a filter of our greatest environmental exposure - the foods we consume. It is now clear that we each experience a given meal differently, based on our unique gut microbial communities...
November 27, 2017: Adipocyte
https://www.readbyqxmd.com/read/29171095/the-gastrointestinal-microbiome-a-review
#20
REVIEW
P C Barko, M A McMichael, K S Swanson, D A Williams
The gastrointestinal microbiome is a diverse consortium of bacteria, archaea, fungi, protozoa, and viruses that inhabit the gut of all mammals. Studies in humans and other mammals have implicated the microbiome in a range of physiologic processes that are vital to host health including energy homeostasis, metabolism, gut epithelial health, immunologic activity, and neurobehavioral development. The microbial genome confers metabolic capabilities exceeding those of the host organism alone, making the gut microbiome an active participant in host physiology...
November 24, 2017: Journal of Veterinary Internal Medicine
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