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Genomics and Obesity

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https://www.readbyqxmd.com/read/27907186/inter-tissue-gene-co-expression-networks-between-metabolically-healthy-and-unhealthy-obese-individuals
#1
Lisette J A Kogelman, Jingyuan Fu, Lude Franke, Jan Willem Greve, Marten Hofker, Sander S Rensen, Haja N Kadarmideen
BACKGROUND: Obesity is associated with severe co-morbidities such as type 2 diabetes and nonalcoholic steatohepatitis. However, studies have shown that 10-25 percent of the severely obese individuals are metabolically healthy. To date, the identification of genetic factors underlying the metabolically healthy obese (MHO) state is limited. Systems genetics approaches have led to the identification of genes and pathways in complex diseases. Here, we have used such approaches across tissues to detect genes and pathways involved in obesity-induced disease development...
2016: PloS One
https://www.readbyqxmd.com/read/27900395/microbiome-and-metabolic-disease-revisiting-the-bacterial-phylum-bacteroidetes
#2
REVIEW
Elizabeth L Johnson, Stacey L Heaver, William A Walters, Ruth E Ley
Bacterial species composition in the gut has emerged as an important factor in obesity and its related metabolic diseases such as type 2 diabetes. Out of thousands of bacterial species-level phylotypes inhabiting the human gut, the majority belong to two dominant phyla, the Bacteroidetes and Firmicutes. Members of the Bacteroidetes in particular have been associated with human metabolic diseases. However, their associations with disease are not always consistent between studies. Delving deeper into the diversity within the Bacteroidetes reveals a vast diversity in genomes and capacities, which partly explain how not all members respond equally to similar environmental conditions in their hosts...
November 29, 2016: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/27895808/mendelian-inheritance-of-trimodal-cpg-methylation-sites-suggests-distal-cis-acting-genetic-effects
#3
Shaza B Zaghlool, Mashael Al-Shafai, Wadha A Al Muftah, Pankaj Kumar, Christian Gieger, Melanie Waldenberger, Mario Falchi, Karsten Suhre
BACKGROUND: Environmentally influenced phenotypes, such as obesity and insulin resistance, can be transmitted over multiple generations. Epigenetic modifications, such as methylation of DNA cytosine-guanine (CpG) pairs, may be carriers of inherited information. At the population level, the methylation state of such "heritable" CpG sites is expected to follow a trimodal distribution, and their mode of inheritance should be Mendelian. METHODS: Using the Illumina Infinium 450 K DNA methylation array, we determined DNA CpG-methylation in blood cells from a family cohort 123 individuals of Arab ethnicity, including 18 elementary father-mother-child trios, we asked whether Mendelian inheritance of CpG methylation is observed, and most importantly, whether it is independent of any genetic signals...
2016: Clinical Epigenetics
https://www.readbyqxmd.com/read/27895803/time-course-microarray-analysis-for-identifying-candidate-genes-involved-in-obesity-associated-pathological-changes-in-the-mouse-colon
#4
Yun Jung Bae, Sung-Eun Kim, Seong Yeon Hong, Taesun Park, Sang Gyu Lee, Myung-Sook Choi, Mi-Kyung Sung
BACKGROUND: Obesity is known to increase the risk of colorectal cancer. However, mechanisms underlying the pathogenesis of obesity-induced colorectal cancer are not completely understood. The purposes of this study were to identify differentially expressed genes in the colon of mice with diet-induced obesity and to select candidate genes as early markers of obesity-associated abnormal cell growth in the colon. METHODS: C57BL/6N mice were fed normal diet (11% fat energy) or high-fat diet (40% fat energy) and were euthanized at different time points...
2016: Genes & Nutrition
https://www.readbyqxmd.com/read/27894254/divergent-selection-induced-obesity-alters-the-composition-and-functional-pathways-of-chicken-gut-microbiota
#5
Jinmei Ding, Lele Zhao, Lifeng Wang, Wenjing Zhao, Zhengxiao Zhai, Li Leng, Yuxiang Wang, Chuan He, Yan Zhang, Heping Zhang, Hui Li, He Meng
BACKGROUND: The gastrointestinal tract is populated by a complex and vast microbial network, with a composition that reflects the relationships of the symbiosis, co-metabolism, and co-evolution of these microorganisms with their host. The mechanism that underlies such interactions between the genetics of the host and gut microbiota remains elusive. RESULTS: To understand how genetic variation of the host shapes the gut microbiota and interacts with it to affect the metabolic phenotype of the host, we compared the abundance of microbial taxa and their functional performance between two lines of chickens (fat and lean) that had undergone long-term divergent selection for abdominal fat pad weight, which resulted in a 4...
November 28, 2016: Genetics, Selection, Evolution: GSE
https://www.readbyqxmd.com/read/27893783/role-of-pten-in-oxidative-stress-and-dna-damage-in-the-liver-of-whole-body-pten-haplodeficient-mice
#6
Ezgi Eyluel Bankoglu, Oliver Tschopp, Johannes Schmitt, Philipp Burkard, Daniel Jahn, Andreas Geier, Helga Stopper
Type 2 diabetes (T2DM) and obesity are frequently associated with non-alcoholic fatty liver disease (NAFLD) and with an elevated cancer incidence. The molecular mechanisms of carcinogenesis in this context are only partially understood. High blood insulin levels are typical in early T2DM and excessive insulin can cause elevated reactive oxygen species (ROS) production and genomic instability. ROS are important for various cellular functions in signaling and host defense. However, elevated ROS formation is thought to be involved in cancer induction...
2016: PloS One
https://www.readbyqxmd.com/read/27889186/circadian-homeostasis-of-liver-metabolism-suppresses-hepatocarcinogenesis
#7
Nicole M Kettner, Horatio Voicu, Milton J Finegold, Cristian Coarfa, Arun Sreekumar, Nagireddy Putluri, Chinenye A Katchy, Choogon Lee, David D Moore, Loning Fu
Chronic jet lag induces spontaneous hepatocellular carcinoma (HCC) in wild-type mice following a mechanism very similar to that observed in obese humans. The process initiates with non-alcoholic fatty liver disease (NAFLD) that progresses to steatohepatitis and fibrosis before HCC detection. This pathophysiological pathway is driven by jet-lag-induced genome-wide gene deregulation and global liver metabolic dysfunction, with nuclear receptor-controlled cholesterol/bile acid and xenobiotic metabolism among the top deregulated pathways...
November 14, 2016: Cancer Cell
https://www.readbyqxmd.com/read/27888582/nucleotide-substitutions-in-cd101-the-human-homolog-of-a-diabetes-susceptibility-gene-in-non-obese-diabetic-mouse-in-patients-with-type-1-diabetes
#8
Misako Okuno, Yoshihito Kasahara, Masafumi Onodera, Noriyuki Takubo, Michiko Okajima, Shigeru Suga, Nobuyuki Watanabe, Junichi Suzuki, Tadayuki Ayabe, Tatsuhiko Urakami, Tomoyuki Kawamura, Nobuyuki Kikuchi, Ichiro Yokota, Toru Kikuchi, Shin Amemiya, Kazuhiko Nakabayashi, Keiko Hayashi, Kenichiro Hata, Yoichi Matsubara, Tsutomu Ogata, Maki Fukami, Shigetaka Sugihara
AIMS/INTRODUCTION: Although genome-wide association studies have identified more than 50 susceptibility genes for type 1 diabetes, low-frequency risk variants could remain unrecognized. The present study aimed to identify novel type 1 diabetes susceptibility genes by newly established methods. MATERIALS AND METHODS: We carried out whole-exome sequencing and genome-wide copy-number analysis for a Japanese family consisting of two patients with type 1 diabetes and three unaffected relatives...
October 19, 2016: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/27881840/a-combined-linkage-and-association-strategy-identifies-a-variant-near-the-gstp1-gene-associated-with-bmi-in-the-mexican-population
#9
Hugo Villamil-Ramírez, Paola León-Mimila, Luis R Macias-Kauffer, Adrián Canizalez-Román, Marisela Villalobos-Comparán, Nidia León-Sicairos, Joel Vega-Badillo, Fausto Sánchez-Muñoz, Blanca López-Contreras, Sofía Morán-Ramos, Teresa Villarreal-Molina, Luis C Zurita, Francisco Campos-Pérez, Adriana Huertas-Vazquez, Rafael Bojalil, Sandra Romero-Hidalgo, Carlos A Aguilar-Salinas, Samuel Canizales-Quinteros
Obesity is a major public health concern in Mexico and worldwide. Although the estimated heritability is high, common variants identified by genome-wide association studies explain only a small proportion of this heritability. A combination of linkage and association strategies could be a more robust and powerful approach to identify other obesity-susceptibility variants. We thus sought to identify novel genetic variants associated with obesity-related traits in the Mexican population by combining these methods...
November 24, 2016: Journal of Human Genetics
https://www.readbyqxmd.com/read/27881521/is-famine-exposure-during-developmental-life-in-rural-bangladesh-associated-with-a-metabolic-and-epigenetic-signature-in-young-adulthood-a-historical-cohort-study
#10
S Finer, M S Iqbal, R Lowe, B W Ogunkolade, S Pervin, C Mathews, M Smart, D S Alam, G A Hitman
OBJECTIVES: Famine exposure in utero can 'programme' an individual towards type 2 diabetes and obesity in later life. We sought to identify, (1) whether Bangladeshis exposed to famine during developmental life are programmed towards diabetes and obesity, (2) whether this programming was specific to gestational or postnatal exposure windows and (3) whether epigenetic differences were associated with famine exposure. DESIGN: A historical cohort study was performed as part of a wider cross-sectional survey...
November 23, 2016: BMJ Open
https://www.readbyqxmd.com/read/27867202/generalization-and-fine-mapping-of-european-ancestry-based-central-adiposity-variants-in-african-ancestry-populations
#11
S Yoneyama, J Yao, X Guo, L Fernandez-Rhodes, U Lim, J Boston, P Buzková, C S Carlson, I Cheng, B Cochran, R Cooper, G Ehret, M Fornage, J Gong, M Gross, C C Gu, J Haessler, C A Haiman, B Henderson, L A Hindorff, D Houston, M R Irvin, R Jackson, L Kuller, M Leppert, C E Lewis, R Li, L Le Marchand, T C Matise, K-Dh Nguyen, A Chakravarti, J S Pankow, N Pankratz, L Pooler, M D Ritchie, S A Bien, C L Wassel, Y-DI Chen, K D Taylor, M Allison, J I Rotter, P J Schreiner, F Schumacher, L Wilkens, E Boerwinkle, C Kooperberg, U Peters, S Buyske, M Graff, K E North
BACKGROUND/OBJECTIVES: Central adiposity measures such as waist circumference (WC) and waist-to-hip ratio (WHR) are associated with cardiometabolic disorders independently of BMI and are gaining clinically utility. Several studies report genetic variants associated with central adiposity, but most utilize only European ancestry populations. Understanding whether the genetic associations discovered among mainly European descendants are shared with African ancestry populations will help elucidate the biological underpinnings of abdominal fat deposition...
November 21, 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/27858497/high-fat-diet-and-exercise-lead-to-a-disrupted-and-pathogenic-dna-methylome-in-mouse-liver
#12
Dan Zhou, Ryan A Hlady, Marissa J Schafer, Thomas A White, Chen Liu, Jeong-Hyeon Choi, Jordan D Miller, Lewis R Roberts, Nathan K LeBrasseur, Keith D Robertson
High-fat diet consumption and sedentary life style elevates risk for obesity, non-alcoholic fatty liver disease, and cancer. Exercise training conveys health benefits in populations with or without these chronic conditions. Diet and exercise regulate gene expression by mediating epigenetic mechanisms in many tissues; however, such effects are poorly documented in the liver, a central metabolic organ. To dissect the consequences of diet and exercise on the liver epigenome, we measured DNA methylation, using reduced representation bisulfite sequencing, and transcription, using RNA-seq, in mice maintained on a fast food diet with sedentary lifestyle or exercise, compared to control diet with and without exercise...
November 18, 2016: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/27843010/identifying-sensitive-windows-for-prenatal-particulate-air-pollution-exposure-and-mitochondrial-dna-content-in-cord-blood
#13
Maria José Rosa, Allan C Just, Marco Sánchez Guerra, Itai Kloog, Hsiao-Hsien Leon Hsu, Kasey J Brennan, Adriana Mercado García, Brent Coull, Rosalind J Wright, Martha María Téllez Rojo, Andrea A Baccarelli, Robert O Wright
INTRODUCTION: Changes in mitochondrial DNA (mtDNA) can serve as a marker of cumulative oxidative stress (OS) due to the mitochondria's unique genome and relative lack of repair systems. In utero particulate matter ≤2.5μm (PM2.5) exposure can enhance oxidative stress. Our objective was to identify sensitive windows to predict mtDNA damage experienced in the prenatal period due to PM2.5 exposure using mtDNA content measured in cord blood. MATERIAL AND METHODS: Women affiliated with the Mexican social security system were recruited during pregnancy in the Programming Research in Obesity, Growth, Environment and Social Stressors (PROGRESS) study...
November 11, 2016: Environment International
https://www.readbyqxmd.com/read/27835940/whole-genome-sequence-analysis-of-the-tallyho-jng-mouse
#14
James Denvir, Goran Boskovic, Jun Fan, Donald A Primerano, Jacaline K Parkman, Jung Han Kim
BACKGROUND: The TALLYHO/Jng (TH) mouse is a polygenic model for obesity and type 2 diabetes first described in the literature in 2001. The origin of the TH strain is an outbred colony of the Theiler Original strain and mice derived from this source were selectively bred for male hyperglycemia establishing an inbred strain at The Jackson Laboratory. TH mice manifest many of the disease phenotypes observed in human obesity and type 2 diabetes. RESULTS: We sequenced the whole genome of TH mice maintained at Marshall University to a depth of approximately 64...
November 11, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27832776/mapping-genetic-research-in-non-communicable-disease-publications-in-selected-arab-countries-first-step-towards-a-guided-research-agenda
#15
REVIEW
Zeina Jamaluddine, Abla Mehio Sibai, Shahd Othman, Soha Yazbek
BACKGROUND: In the Arab world, intervention and policy response to non-communicable diseases (NCD) has been weak despite extensive epidemiological evidence highlighting the alarmingly increased prevalence of chronic diseases. Generating genetic information is one key component to promote efficient disease management strategies. This study undertook a scoping review to generate the profile of the undertaken research on genetics of NCD publications in selected Arab countries. An analysis of the research produced examined the extent, range, nature, topic and methods of published research...
November 10, 2016: Health Research Policy and Systems
https://www.readbyqxmd.com/read/27832418/obesity-as-a-risk-factor-for-malignant-melanoma-and-non-melanoma-skin-cancer
#16
REVIEW
K Karimi, T H Lindgren, C A Koch, Robert T Brodell
The dramatic increases in incidence of both obesity and many cancers including skin cancer emphasize the need to better understand the pathophysiology of both conditions and their connections. Melanoma is considered the fastest growing cancer and rates of non-melanoma skin cancer have also increased over the last decade. The molecular mechanisms underlying the association between obesity and skin cancer are not clearly understood but emerging evidence points to changes in the tumor microenvironment including aberrant cell signaling and genomic instability in the chronic inflammatory state many obese individuals experience...
November 10, 2016: Reviews in Endocrine & Metabolic Disorders
https://www.readbyqxmd.com/read/27829173/multiple-pathways-of-sirt6-at-the-crossroads-in-the-control-of-longevity-cancer-and-cardiovascular-diseases
#17
REVIEW
Milena Vitiello, Alberto Zullo, Luigi Servillo, Francesco Paolo Mancini, Adriana Borriello, Alfonso Giovane, Fulvio Della Ragione, Nunzia D'Onofrio, Maria Luisa Balestrieri
Sirtuin 6 (SIRT6) is a member of the sirtuin family NAD(+)-dependent deacetylases with multiple roles in controlling organism homeostasis, lifespan, and diseases. Due to its complex and opposite functional roles, this sirtuin is considered a two-edged sword in health and disease. Indeed, SIRT6 improves longevity, similarly to the founding yeast member, silent information regulator-2 (Sir2), and modulates genome stability, telomere integrity, transcription, and DNA repair. Its deficiency is associated with chronic inflammation, diabetes, cardiac hypertrophy, obesity, liver dysfunction, muscle/adipocyte disorders, and cancer...
November 6, 2016: Ageing Research Reviews
https://www.readbyqxmd.com/read/27822554/farnesoid-x-receptor-signaling-shapes-the-gut-microbiota-and-controls-hepatic-lipid-metabolism
#18
Limin Zhang, Cen Xie, Robert G Nichols, Siu H J Chan, Changtao Jiang, Ruixin Hao, Philip B Smith, Jingwei Cai, Margaret N Simons, Emmanuel Hatzakis, Costas D Maranas, Frank J Gonzalez, Andrew D Patterson
The gut microbiota modulates obesity and associated metabolic phenotypes in part through intestinal farnesoid X receptor (FXR) signaling. Glycine-β-muricholic acid (Gly-MCA), an intestinal FXR antagonist, has been reported to prevent or reverse high-fat diet (HFD)-induced and genetic obesity, insulin resistance, and fatty liver; however, the mechanism by which these phenotypes are improved is not fully understood. The current study investigated the influence of FXR activity on the gut microbiota community structure and function and its impact on hepatic lipid metabolism...
September 2016: MSystems
https://www.readbyqxmd.com/read/27819203/nutrigenomics-in-the-modern-era
#19
John C Mathers
The concept that interactions between nutrition and genetics determine phenotype was established by Garrod at the beginning of the 20th century through his ground-breaking work on inborn errors of metabolism. A century later, the science and technologies involved in sequencing of the human genome stimulated development of the scientific discipline which we now recognise as nutritional genomics (nutrigenomics). Much of the early hype around possible applications of this new science was unhelpful and raised expectations, which have not been realised as quickly as some would have hoped...
November 7, 2016: Proceedings of the Nutrition Society
https://www.readbyqxmd.com/read/27815534/biological-roles-of-micrornas-in-the-control-of-insulin-secretion-and-action
#20
Sophie Calderari, Malika Diawara, Alois Garaud, Dominique Gauguier
MicroRNAs (miRNAs) are intracellular and circulating molecular components contributing to genome expression control through binding mRNA targets, which generally results in downregulated mRNA expression. One miRNA can target several mRNAs and one transcript can be targeted by several miRNAs, resulting in complex fine tuning of regulation of gene networks and signaling pathways. miRNAs regulate metabolism, adipocyte differentiation, pancreatic development, β-cell mass, insulin biosynthesis, secretion and signaling and their role in diabetes and obesity is emerging...
November 4, 2016: Physiological Genomics
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