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Genomics and Obesity

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https://www.readbyqxmd.com/read/28224759/genomic-variants-at-20p11-associated-with-body-fat-mass-in-the-european-population
#1
Yu-Fang Pei, Hai-Gang Ren, Lu Liu, Xiao Li, Chen Fang, Yun Huang, Wen-Zhu Hu, Wei-Wen Kong, An-Ping Feng, Xin-Yi You, Wen Zhao, Hui Shen, Qing Tian, Yong-Hong Zhang, Hong-Wen Deng, Lei Zhang
OBJECTIVE: Body fat mass (BFM) is more homogeneous and accurate than body total mass in measuring obesity but has rarely been studied. Aiming to uncover the genetic basis of fat-induced obesity, a genome-wide association meta-analysis of BFM, after adjustment by body lean mass, was performed in the European population. METHODS: Three samples of European ancestry were included in the meta-analysis: the Framingham Heart Study (N = 6,004), the Kansas City osteoporosis study (N = 2,207), and the Omaha osteoporosis study (N = 968)...
February 22, 2017: Obesity
https://www.readbyqxmd.com/read/28223964/mouse-models-of-human-gwas-hits-for-obesity-and-diabetes-in-the-post-genomic-era-time-for-reevaluation
#2
Samantha Laber, Roger D Cox
No abstract text is available yet for this article.
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28223936/two-pore-channels-catalyzers-of-endolysosomal-transport-and-function
#3
REVIEW
Christian Grimm, Cheng-Chang Chen, Christian Wahl-Schott, Martin Biel
Two-pore channels (TPCs) have recently emerged as a novel class of non-selective cation channels in the endolysosomal system. There are two members in the human genome, TPC1 and TPC2. Studies with TPC knockout and knockdown models have revealed that these channels participate in the regulation of multiple endolysosomal trafficking pathways which when dysregulated can lead to or influence the development of a range of different diseases such as lysosomal storage, metabolic, or infectious diseases. TPCs have been demonstrated to be activated by different endogenous stimuli, PI(3,5)P2 and NAADP, and ATP has been found to block TPC activation via mTOR...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28222718/abnormal-epigenetic-changes-during-differentiation-of-human-skeletal-muscle-stem-cells-from-obese-subjects
#4
Cajsa Davegårdh, Christa Broholm, Alexander Perfilyev, Tora Henriksen, Sonia García-Calzón, Lone Peijs, Ninna Schiøler Hansen, Petr Volkov, Rasmus Kjøbsted, Jørgen F P Wojtaszewski, Maria Pedersen, Bente Klarlund Pedersen, Dov B Ballak, Charles A Dinarello, Bas Heinhuis, Leo A B Joosten, Emma Nilsson, Allan Vaag, Camilla Scheele, Charlotte Ling
BACKGROUND: Human skeletal muscle stem cells are important for muscle regeneration. However, the combined genome-wide DNA methylation and expression changes taking place during adult myogenesis have not been described in detail and novel myogenic factors may be discovered. Additionally, obesity is associated with low relative muscle mass and diminished metabolism. Epigenetic alterations taking place during myogenesis might contribute to these defects. METHODS: We used Infinium HumanMethylation450 BeadChip Kit (Illumina) and HumanHT-12 Expression BeadChip (Illumina) to analyze genome-wide DNA methylation and transcription before versus after differentiation of primary human myoblasts from 14 non-obese and 14 obese individuals...
February 22, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28219716/genetic-regulation-of-differentially-methylated-genes-in-visceral-adipose-tissue-of-severely-obese-men-discordant-for-the-metabolic-syndrome
#5
Frédéric Guénard, André Tchernof, Yves Deshaies, Simon Biron, Odette Lescelleur, Laurent Biertho, Simon Marceau, Louis Pérusse, Marie-Claude Vohl
A genetic influence on methylation levels has been reported and methylation quantitative trait loci (meQTL) have been identified in various tissues. The contribution of genetic and epigenetic factors in the development of the metabolic syndrome (MetS) has also been noted. To pinpoint candidate genes for testing the association of SNPs with MetS and its components, we aimed to evaluate the contribution of genetic variations to differentially methylated CpG sites in severely obese men discordant for MetS. A genome-wide differential methylation analysis was conducted in visceral adipose tissue (VAT) of 31 severely obese men discordant for MetS (16 with and 15 without MetS) and identified ∼17,800 variable CpG sites...
February 2, 2017: Translational Research: the Journal of Laboratory and Clinical Medicine
https://www.readbyqxmd.com/read/28216432/epigenetic-modification-by-dietary-factors-implications-in-metabolic-syndrome
#6
REVIEW
Jae-Ho Park, Soon-Hee Kim, Myeong Soo Lee, Myung-Sunny Kim
Dietary factors play a role in normal biological processes and are involved in the regulation of pathological progression over a lifetime. Evidence has emerged indicating that dietary factor-dependent epigenetic modifications can significantly affect genome stability and the expression of mRNA and proteins, which are involved in metabolic dysfunction. Since metabolic syndrome is a progressive phenotype characterized by insulin resistance, obesity, hypertension, dyslipidemia, or type 2 diabetes, gene-diet interactions are important processes involved in the initiation of particular symptoms of metabolic syndrome and their progression...
February 16, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28214879/thiamine-deprivation-produces-a-liver-atp-deficit-and-metabolic-and-genomic-effects-in-mice-findings-are-parallel-to-those-of-biotin-deficiency-and-have-implications-for-energy-disorders
#7
Alain de J Hernandez-Vazquez, Josue Andres Garcia-Sanchez, Elizabeth Moreno-Arriola, Ana Salvador-Adriano, Daniel Ortega-Cuellar, Antonio Velazquez-Arellano
Thiamine is one of several essential cofactors for ATP generation. Its deficiency, like in beriberi and in the Wernicke-Korsakoff syndrome, has been studied for many decades. However, its mechanism of action is still not completely understood at the cellular and molecular levels. Since it acts as a coenzyme for dehydrogenases of pyruvate, branched-chain keto acids, and ketoglutarate, its nutritional privation is partly a phenocopy of inborn errors of metabolism, among them maple syrup urine disease. In the present paper, we report metabolic and genomic findings in mice deprived of thiamine...
February 18, 2017: Journal of Nutrigenetics and Nutrigenomics
https://www.readbyqxmd.com/read/28214526/recent-advances-in-human-genetics-and-epigenetics-of-adiposity-pathway-to-precision-medicine
#8
Tove Fall, Michael Mendelson, Elizabeth K Speliotes
Obesity is a heritable trait that contributes to substantial global morbidity and mortality. Here, we summarize findings from the last decade of genetic and epigenetic research focused on unravelling the underpinnings of adiposity. More than 140 genetic regions are now known to influence adiposity traits. The genetics of general adiposity, as measured by body mass index, and that of abdominal obesity, as measured by waist to hip ratio, have distinct biological backgrounds. Expression of genes associated with general adiposity are enriched in the nervous system...
February 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28211912/dna-methylation-map-in-circulating-leukocytes-mirrors-subcutaneous-adipose-tissue-methylation-pattern-a-genome-wide-analysis-from-non-obese-and-obese-patients
#9
A B Crujeiras, A Diaz-Lagares, J Sandoval, F I Milagro, S Navas-Carretero, M C Carreira, A Gomez, D Hervas, M P Monteiro, F F Casanueva, M Esteller, J A Martinez
The characterization of the epigenetic changes within the obesity-related adipose tissue will provide new insights to understand this metabolic disorder, but adipose tissue is not easy to sample in population-based studies. We aimed to evaluate the capacity of circulating leukocytes to reflect the adipose tissue-specific DNA methylation status of obesity susceptibility. DNA samples isolated from subcutaneous adipose tissue and circulating leukocytes were hybridized in the Infinium HumanMethylation 450 BeadChip...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28207535/an-investigation-of-obesity-susceptibility-genes-in-northern-han-chinese-by-targeted-resequencing
#10
Yili Wu, Weijing Wang, Wenjie Jiang, Jie Yao, Dongfeng Zhang
Our earlier genome-wide linkage study of body mass index (BMI) showed strong signals from 7q36.3 and 8q21.13. This case-control study set to investigate 2 genomic regions which may harbor variants contributed to development of obesity.We employed targeted resequencing technology to detect single nucleotide polymorphisms (SNPs) in 7q36.3 and 8q21.13 from 16 individuals with obesity. These were compared with 504 East Asians in the 1000 Genomes Project as a reference panel. Linkage disequilibrium (LD) block analysis was performed for the significant SNPs located near the same gene...
February 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28201990/a-vast-genomic-deletion-in-the-c56bl-6-genome-affects-different-genes-within-the-ifi200-cluster-on-chromosome-1-and-mediates-obesity-and-insulin-resistance
#11
Heike Vogel, Markus Jähnert, Mandy Stadion, Daniela Matzke, Stephan Scherneck, Annette Schürmann
BACKGROUND: Obesity, the excessive accumulation of body fat, is a highly heritable and genetically heterogeneous disorder. The complex, polygenic basis for the disease consisting of a network of different gene variants is still not completely known. RESULTS: In the current study we generated a BAC library of the obese-prone NZO strain to clarify the genomic alteration within the gene cluster Ifi200 on chr.1 including Ifi202b, an obesity gene that is in contrast to NZO not expressed in the lean B6 mouse...
February 15, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28199197/childhood-cancers-and-systems-medicine
#12
William L Stone, Kathryn J Klopfenstein, M J Hajianpour, Marcela I Popescu, Cathleen M Cook, Koymangalath Krishnan
Despite major advances in treatment, pediatric cancers in the 5-16 age group remain the most common cause of disease death, and one out of eight children with cancer will not survive. Among children that do survive, some 60% suffer from late effects such as cancer recurrence and increased risk of obesity. This paper will provide a broad overview of pediatric oncology in the context of systems medicine. Systems medicine utilizes an integrative approach that relies on patient information gained from omics technology...
March 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28196965/genomic-microdiversity-of-bifidobacterium-pseudocatenulatum-underlying-differential-strain-level-responses-to-dietary-carbohydrate-intervention
#13
Guojun Wu, Chenhong Zhang, Huan Wu, Ruirui Wang, Jian Shen, Linghua Wang, Yufeng Zhao, Xiaoyan Pang, Xiaojun Zhang, Liping Zhao, Menghui Zhang
The genomic basis of the response to dietary intervention of human gut beneficial bacteria remains elusive, which hinders precise manipulation of the microbiota for human health. After receiving a dietary intervention enriched with nondigestible carbohydrates for 105 days, a genetically obese child with Prader-Willi syndrome lost 18.4% of his body weight and showed significant improvement in his bioclinical parameters. We obtained five isolates (C1, C15, C55, C62, and C95) of one of the most abundantly promoted beneficial species, Bifidobacterium pseudocatenulatum, from a postintervention fecal sample...
February 14, 2017: MBio
https://www.readbyqxmd.com/read/28194004/genetic-contributions-to-self-reported-tiredness
#14
V Deary, S P Hagenaars, S E Harris, W D Hill, G Davies, D C M Liewald, A M McIntosh, C R Gale, I J Deary
Self-reported tiredness and low energy, often called fatigue, are associated with poorer physical and mental health. Twin studies have indicated that this has a heritability between 6 and 50%. In the UK Biobank sample (N=108 976), we carried out a genome-wide association study (GWAS) of responses to the question, 'Over the last two weeks, how often have you felt tired or had little energy?' Univariate GCTA-GREML found that the proportion of variance explained by all common single-nucleotide polymorphisms for this tiredness question was 8...
February 14, 2017: Molecular Psychiatry
https://www.readbyqxmd.com/read/28186371/gene-expression-and-epigenetic-aberrations-in-f1-placentas-fathered-by-obese-males
#15
Megan Mitchell, Reiner Strick, Pamela L Strissel, Ralf Dittrich, Nicole O McPherson, Michelle Lane, Galyna Pliushch, Ramya Potabattula, Thomas Haaf, Nady El Hajj
Gene expression and/or epigenetic deregulation may have consequences for sperm and blastocysts, as well as for the placenta, together potentially contributing to problems observed in offspring. We previously demonstrated specific perturbations of fertilization, blastocyst formation, implantation, as well as aberrant glucose metabolism and adiposity in offspring using a mouse model of paternal obesity. The current investigation analysed gene expression and methylation of specific CpG residues in F1 placentas of pregnancies fathered by obese and normal-weight male mice, using real-time PCR and bisulfite pyrosequencing...
February 10, 2017: Molecular Reproduction and Development
https://www.readbyqxmd.com/read/28181539/dissecting-the-brown-adipogenic-regulatory-network-using-integrative-genomics
#16
Rachana N Pradhan, Johannes J Bues, Vincent Gardeux, Petra C Schwalie, Daniel Alpern, Wanze Chen, Julie Russeil, Sunil K Raghav, Bart Deplancke
Brown adipocytes regulate energy expenditure via mitochondrial uncoupling, which makes them attractive therapeutic targets to tackle obesity. However, the regulatory mechanisms underlying brown adipogenesis are still poorly understood. To address this, we profiled the transcriptome and chromatin state during mouse brown fat cell differentiation, revealing extensive gene expression changes and chromatin remodeling, especially during the first day post-differentiation. To identify putatively causal regulators, we performed transcription factor binding site overrepresentation analyses in active chromatin regions and prioritized factors based on their expression correlation with the bona-fide brown adipogenic marker Ucp1 across multiple mouse and human datasets...
February 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28174120/xenobiotics-and-the-glucocorticoid-receptor
#17
REVIEW
Linda S M Gulliver
Glucocorticoid Receptor (GR) is present in virtually every human cell type. Representing a nuclear receptor superfamily, GR has several different isoforms essentially acting as ligand-dependent transcription factors, regulating glucocorticoid-responsive gene expression in both a positive and a negative manner. Although the natural ligand of the Glucocorticoid Receptor, glucocorticoids (GC) represent only some of the multiple ligands for GR. Xenobiotics, ubiquitous in the environment, bind to GR and are also capable of activating or repressing GR gene expression, thereby modulating GR cell and tissue-specific downstream effects in a multitude of ways that include responses to inflammatory, allergic, metabolic, neoplastic and autoimmune processes...
February 4, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28170448/genome-wide-analysis-identifies-colonic-genes-differentially-associated-with-serum-leptin-and-insulin-concentrations-in-c57bl-6j-mice-fed-a-high-fat-diet
#18
Sung-Eun Kim, Jinsil Choo, Joon Yoon, Jae Ryang Chu, Yun Jung Bae, Seungyeoun Lee, Taesung Park, Mi-Kyung Sung
Obesity-induced chronic inflammation is known to increase the risk of ulcerative colitis, Crohn's disease, and colorectal cancer. Accumulating evidence suggests that leptin and insulin are key molecules linking obesity with diseases of the lower intestine. Here, we identified serum phenotype-associated genes in the colon of diet-induced obese mice as early biomarkers of obesity-associated colonic diseases. C57BL/6J mice were fed with either normal diet (ND, 15% of fat calories) or high-fat diet (HFD, 45% of fat calories) for 8 weeks...
2017: PloS One
https://www.readbyqxmd.com/read/28168960/sex-specific-neurodevelopmental-programming-by-placental-insulin-receptors-on-stress-reactivity-and-sensorimotor-gating
#19
Stefanie L Bronson, Jennifer C Chan, Tracy L Bale
BACKGROUND: Diabetes, obesity, and overweight are prevalent pregnancy complications that predispose offspring to neurodevelopmental disorders, including autism, attention-deficit/hyperactivity disorder, and schizophrenia. Although male individuals are three to four times more likely than female individuals to develop these disorders, the mechanisms driving the sex specificity of disease vulnerability remain unclear. Because defective placental insulin receptor (InsR) signaling is a hallmark of pregnancy metabolic dysfunction, we hypothesized that it may be an important contributor and novel mechanistic link to sex-specific neurodevelopmental changes underlying disease risk...
December 30, 2016: Biological Psychiatry
https://www.readbyqxmd.com/read/28166748/body-mass-index-modifies-the-relationship-between-%C3%AE-h2ax-a-dna-damage-biomarker-and-pathological-complete-response-in-triple-negative-breast-cancer
#20
Maddalena Barba, Patrizia Vici, Laura Pizzuti, Luigi Di Lauro, Domenico Sergi, Anna Di Benedetto, Cristiana Ercolani, Francesca Sperati, Irene Terrenato, Claudio Botti, Lucia Mentuccia, Laura Iezzi, Teresa Gamucci, Clara Natoli, Ilio Vitale, Marcella Mottolese, Ruggero De Maria, Marcello Maugeri-Saccà
BACKGROUND: Body mass index (BMI) is largely investigated as a prognostic and predictive factor in triple-negative breast cancer (TNBC). Overweight and obesity are linked to a variety of pathways regulating tumor-promoting functions, including the DNA damage response (DDR). The DDR physiologically safeguards genome integrity but, in a neoplastic background, it is aberrantly engaged and protects cancer cells from chemotherapy. We herein verified the role of BMI on a previously assessed association between DDR biomarkers and pathological complete response (pCR) in TNBC patients treated with neoadjuvant chemotherapy (NACT)...
February 6, 2017: BMC Cancer
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