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Genomics and Obesity

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https://www.readbyqxmd.com/read/28326685/hugonella-massiliensis-gen-nov-sp-nov-genome-sequence-and-description-of-a-new-strictly-anaerobic-bacterium-isolated-from-the-human-gut
#1
Ziena Elsawi, Amadou Hamidou Togo, Mamadou Beye, Grégory Dubourg, Claudia Andrieu, Nicholas Armsrtong, Magali Richez, Fabrizio di Pinto, Fadi Bittar, Noémie Labas, Pierre-Edouard Fournier, Didier Raoult, Saber Khelaifia
The human gut is composed of a large diversity of microorganisms, which have been poorly described. Here, using culturomics, a new concept based on the variation in culture conditions and MALDI-TOF MS identification, we proceed to explore the microbial diversity of the complex ecosystem of the human gut. Using this approach, we isolated strain AT8(T) (=CSUR P2118 =  DSM 101782) from stool specimens collected from a 51-year-old obese French woman. Strain AT8(T) is a strictly anaerobic, nonmotile, nonspore-forming gram-positive coccus that do not exhibit catalase and oxidase activities...
March 21, 2017: MicrobiologyOpen
https://www.readbyqxmd.com/read/28321693/age-at-diagnosis-obesity-smoking-and-molecular-subtypes-in-muscle-invasive-bladder-cancer
#2
Xuezheng Sun, Katherine A Hoadley, William Y Kim, Helena Furberg, Andrew F Olshan, Melissa A Troester
BACKGROUND: Heterogeneity of muscle-invasive bladder cancer (MIBC) has been characterized using whole-genome mRNA expression data, showing distinct molecular and clinicopathological characteristics by subtypes. However, associations between risk factors and molecular subtypes have not been reported. METHODS: Four previously published schemes were used to categorize molecular subtypes in 372 MIBC patients from the Cancer Genome Atlas (TCGA). Data on gene expression (RNA-seq), demographic, and clinicopathological characteristics were retrieved through TCGA data portal...
March 20, 2017: Cancer Causes & Control: CCC
https://www.readbyqxmd.com/read/28320971/neuroendocrine-androgen-action-is-a-key-extraovarian-mediator-in-the-development-of-polycystic-ovary-syndrome
#3
Aimee S L Caldwell, Melissa C Edwards, Reena Desai, Mark Jimenez, Robert B Gilchrist, David J Handelsman, Kirsty A Walters
Polycystic ovary syndrome (PCOS) is a complex hormonal disorder characterized by reproductive, endocrine, and metabolic abnormalities. As the origins of PCOS remain unknown, mechanism-based treatments are not feasible and current management relies on treatment of symptoms. Hyperandrogenism is the most consistent PCOS characteristic; however, it is unclear whether androgen excess, which is treatable, is a cause or a consequence of PCOS. As androgens mediate their actions via the androgen receptor (AR), we combined a mouse model of dihydrotestosterone (DHT)-induced PCOS with global and cell-specific AR-resistant (ARKO) mice to investigate the locus of androgen actions that mediate the development of the PCOS phenotype...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28320771/the-effect-of-maternal-chromium-status-on-lipid-metabolism-in-female-elderly-mice-offspring-and-involved-molecular-mechanism
#4
Qian Zhang, Xiaofang Sun, Xinhua Xiao, Jia Zheng, Ming Li, Miao Yu, Fan Ping, Zhixin Wang, Cuijuan Qi, Tong Wang, Xiaojing Wang
Maternal malnutrition lead to the incidence of metabolic diseases in offspring. The purpose of this project was to exam whether maternal low chromium could disturb normal lipid metabolism in offspring, altering adipose cell differentiation and leading the incidence of lipid metabolism diseases, including metabolic syndrome and obesity. Female C57BL mice were given a control diet (CD) or a low chromium diet (LCD) during the gestational and lactation periods. After weaning, offspring was fed with CD or LCD. The female offspring were assessed at 32 weeks of age...
March 20, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28298470/genetically-driven-hyperglycemia-increases-risk-of-coronary-artery-disease-separately-from-type-2-diabetes
#5
Jordi Merino, Aaron Leong, Daniel C Posner, Bianca Porneala, Lluís Masana, Josée Dupuis, Jose C Florez
OBJECTIVE: This study tested the hypothesis that genetically raised hyperglycemia increases coronary artery disease (CAD) risk separately from the risk conferred by type 2 diabetes as a whole. RESEARCH DESIGN AND METHODS: We conducted a Mendelian randomization (MR) analysis using summary-level statistics from the largest published meta-analyses of genome-wide association studies (GWAS) for fasting glucose (FG) (n = 133,010 participants free of diabetes) and CAD (n = 63,746 case subjects and 130,681 control subjects) of predominantly European ancestry...
March 15, 2017: Diabetes Care
https://www.readbyqxmd.com/read/28296344/genome-wide-analysis-identifies-an-african-specific-variant-in-sema4d-associated-with-body-mass-index
#6
Guanjie Chen, Ayo P Doumatey, Jie Zhou, Lin Lei, Amy R Bentley, Olufemi Fasanmade, Godfrey Okafor, Benjamin Eghan, Kofi Agyenim-Boateng, Albert Amoah, Clement Adebamowo, Joseph Acheampong, Thomas Johnson, Johnnie Oli, Daniel Shriner, Adebowale A Adeyemo, Charles N Rotimi
OBJECTIVE: The prevalence of obesity varies between ethnic groups. No genome-wide association study (GWAS) for body mass index (BMI) has been conducted in continental Africans. METHODS: We performed a GWAS for BMI in 1,570 West Africans (WA). Replication was conducted in independent samples of WA (n = 1,411) and African Americans (AA) (n = 9,020). RESULTS: We identified a novel genome-wide significant African-specific locus for BMI (SEMA4D, rs80068415; minor allele frequency = 0...
March 13, 2017: Obesity
https://www.readbyqxmd.com/read/28286571/we-are-not-alone-a-case-for-the-human-microbiome-in-extra-intestinal-diseases
#7
EDITORIAL
S Shivaji
BACKGROUND: "Dysbiosis" in the gut microbiome has been implicated in auto-immune diseases, in inflammatory diseases, in some cancers and mental disorders. The challenge is to unravel the cellular and molecular basis of dysbiosis so as to understand the disease manifestation. MAIN BODY: Next generation sequencing and genome enabled technologies have led to the establishment of the composition of gut microbiomes and established that "dysbiosis" is the cause of several diseases...
2017: Gut Pathogens
https://www.readbyqxmd.com/read/28278532/genetics-of-reproductive-aging-from-gonadal-dysgenesis-through-menopause
#8
Swapna Desai, Aleksandar Rajkovic
Reproduction is essential for the survival of the species and is influenced by external factors such as smoking and exposure to chemotherapy as well as chronic disorders such as obesity and autoimmunity. Reproductive senescence, such as menopause, is also dependent on multiple intrinsic genetic factors. Reproductive aging is not isolated from an overall aging process, and several studies strongly support the link between the early age of menopause and mortality. The extreme form of reproductive aging is primary ovarian insufficiency (POI) with prevalence ranging from 1 to 5% of the female population...
March 2017: Seminars in Reproductive Medicine
https://www.readbyqxmd.com/read/28277977/human-liver-epigenetic-alterations-in-non-alcoholic-steatohepatitis-are-related-to-insulin-action
#9
Vanessa D de Mello, Ashok Matte, Alexander Perfilyev, Ville Männistö, Tina Rönn, Emma Nilsson, Pirjo Käkelä, Charlotte Ling, Jussi Pihlajamäki
Both genetic and lifestyle factors contribute to the risk of non-alcoholic steatohepatitis (NASH). Additionally, epigenetic modifications may also play a key role in the pathogenesis of NASH. We therefore investigated liver DNA methylation, as a marker for epigenetic alterations, in individuals with simple steatosis and NASH, and further tested if these alterations were associated with clinical phenotypes. Liver biopsies obtained from 95 obese individuals (age: 49.5±7.7 years, BMI: 43±5.7 kg/m(2), type 2 diabetes [T2D]: 35) as a wedge biopsy during a Roux-en-Y gastric bypass operation were investigated...
February 23, 2017: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/28273479/systems-biology-of-metabolism-a-driver-for-developing-personalized-and-precision-medicine
#10
REVIEW
Jens Nielsen
Systems biology uses mathematical models to analyze large datasets and simulate system behavior. It enables integrative analysis of different types of data and can thereby provide new insight into complex biological systems. Here will be discussed the challenges of using systems medicine for advancing the development of personalized and precision medicine to treat metabolic diseases like insulin resistance, obesity, NAFLD, NASH, and cancer. It will be illustrated how the concept of genome-scale metabolic models can be used for integrative analysis of big data with the objective of identifying novel biomarkers that are foundational for personalized and precision medicine...
March 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28272483/snp-snp-interactions-between-wnt4-and-wnt5a-were-associated-with-obesity-related-traits-in-han-chinese-population
#11
Shan-Shan Dong, Wei-Xin Hu, Tie-Lin Yang, Xiao-Feng Chen, Han Yan, Xiang-Ding Chen, Li-Jun Tan, Qing Tian, Hong-Wen Deng, Yan Guo
Considering the biological roles of WNT4 and WNT5A involved in adipogenesis, we aimed to investigate whether SNPs in WNT4 and WNT5A contribute to obesity related traits in Han Chinese population. Targeted genomic sequence for WNT4 and WNT5A was determined in 100 Han Chinese subjects and tag SNPs were selected. Both single SNP and SNP × SNP interaction association analyses with body mass index (BMI) were evaluated in the 100 subjects and another independent sample of 1,627 Han Chinese subjects. Meta-analyses were performed and multiple testing corrections were carried out using the Bonferroni method...
March 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28266614/a-multi-component-classifier-for-nonalcoholic-fatty-liver-disease-nafld-based-on-genomic-proteomic-and-phenomic-data-domains
#12
G Craig Wood, Xin Chu, George Argyropoulos, Peter Benotti, David Rolston, Tooraj Mirshahi, Anthony Petrick, John Gabrielson, David J Carey, Johanna K DiStefano, Christopher D Still, Glenn S Gerhard
Non-alcoholic fatty liver disease (NAFLD) represents a spectrum of conditions that include steatohepatitis and fibrosis that are thought to emanate from hepatic steatosis. Few robust biomarkers or diagnostic tests have been developed for hepatic steatosis in the setting of obesity. We have developed a multi-component classifier for hepatic steatosis comprised of phenotypic, genomic, and proteomic variables using data from 576 adults with extreme obesity who underwent bariatric surgery and intra-operative liver biopsy...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28265714/a-short-history-of-the-5-ht2c-receptor-from-the-choroid-plexus-to-depression-obesity-and-addiction-treatment
#13
REVIEW
Jose M Palacios, Angel Pazos, Daniel Hoyer
This paper is a personal account on the discovery and characterization of the 5-HT2C receptor (first known as the 5-HT1C receptor) over 30 years ago and how it translated into a number of unsuspected features for a G protein-coupled receptor (GPCR) and a diversity of clinical applications. The 5-HT2C receptor is one of the most intriguing members of the GPCR superfamily. Initially referred to as 5-HT1CR, the 5-HT2CR was discovered while studying the pharmacological features and the distribution of [(3)H]mesulergine-labelled sites, primarily in the brain using radioligand binding and slice autoradiography...
March 7, 2017: Psychopharmacology
https://www.readbyqxmd.com/read/28255832/analysing-algorithms-and-data-sources-for-the-tissue-specific-reconstruction-of-liver-healthy-and-cancer-cells
#14
Jorge Ferreira, Sara Correia, Miguel Rocha
Genome-Scale Metabolic Models (GSMMs), mathematical representations of the cell metabolism in different organisms including humans, are resourceful tools to simulate metabolic phenotypes and understand associated diseases, such as obesity, diabetes and cancer. In the last years, different algorithms have been developed to generate tissue-specific metabolic models that simulate different phenotypes for distinct cell types. Hepatocyte cells are one of the main sites of metabolic conversions, mainly due to their diverse physiological functions...
March 2, 2017: Interdisciplinary Sciences, Computational Life Sciences
https://www.readbyqxmd.com/read/28254843/genetics-of-type-2-diabetes-in-u-s-hispanic-latino-individuals-results-from-the-hispanic-community-health-study-study-of-latinos-hchs-sol
#15
Qibin Qi, Adrienne M Stilp, Tamar Sofer, Jee-Young Moon, Bertha Hidalgo, Adam A Szpiro, Tao Wang, Maggie C Y Ng, Xiuqing Guo, Yii-Der Ida Chen, Kent D Taylor, M Larissa Aviles-Santa, George Papanicolaou, James S Pankow, Neil Schneiderman, Cathy C Laurie, Jerome I Rotter, Robert C Kaplan
Few genome-wide association studies (GWAS) of type 2 diabetes (T2D) have been conducted in US Hispanics/Latinos of diverse backgrounds who are disproportionately affected by diabetes. We conducted a GWAS in 2499 T2D cases and 5247 controls from 6 Hispanic/Latino background groups in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). Our GWAS identified two known loci (TCF7L2 and KCNQ1) reaching genome-wide significance level. Conditional analysis on known index SNPs indicated an additional independent signal at KCNQ1, represented by an African ancestry-specific variant, rs1049549 (OR=1...
March 2, 2017: Diabetes
https://www.readbyqxmd.com/read/28253987/metabolic-syndrome-and-the-cellular-phase-of-alzheimer-s-disease
#16
S Pugazhenthi
Alzheimer's disease (AD) is characterized by cognitive dysfunction and progressive neurodegeneration. The major hallmarks of AD pathology are amyloid plaques and neurofibrillary tangles. However, AD often coexists with other brain microvascular lesions caused by comorbidities, including obesity, diabetes, hypertension, and cardiovascular diseases. The risk factors for these comorbidities are collectively referred to as metabolic syndrome (MetS). Clinical AD is preceded by decades of prodromal cellular phase...
2017: Progress in Molecular Biology and Translational Science
https://www.readbyqxmd.com/read/28253220/fat-mass-and-obesity-associated-protein-attenuates-lipid-accumulation-in-macrophage-foam-cells-and-alleviates-atherosclerosis-in-apolipoprotein-e-deficient-mice
#17
Chunfen Mo, Ming Yang, Xiaojuan Han, Junhong Li, Guangping Gao, Haoran Tai, Ning Huang, Hengyi Xiao
OBJECTIVE: Genome-wide association studies have linked variants of fat mass and obesity-associated protein (FTO) to obesity. However, the molecular function of FTO remains unclear. In this study, we sought to investigate the potential effects of FTO in modulating cholesterol deposition in macrophage foam cells, as well as whether FTO exerts antiatherosclerotic properties in apolipoprotein E-deficient mice. METHOD AND RESULTS: We transfected RAW264.7 cells with plasmids encoding a wild-type or mutant FTO gene (I367F)...
April 2017: Journal of Hypertension
https://www.readbyqxmd.com/read/28250848/tissue-specific-methylation-profile-in-obese-patients-with-type-2-diabetes-before-and-after-roux-en-y-gastric-bypass
#18
REVIEW
Priscila Sala, Raquel Susana Matos de Miranda Torrinhas, Danielle Cristina Fonseca, Graziela Rosa Ravacci, Dan Linetzky Waitzberg, Daniel Giannella-Neto
Eating habits, lifestyles, and exposure to specific environmental factors can greatly impact the risk of developing type 2 diabetes (T2D), influence the genome epigenetically, and affect the expression of genes, including genes related to glycemic control, at any stage of life. The epigenetic mechanism underlying obesity and T2D pathogenesis remains poorly understood. Conventional strategies for the treatment of obesity and its comorbidities often have poor long-term adherence, and pharmacological interventions are limited...
2017: Diabetology & Metabolic Syndrome
https://www.readbyqxmd.com/read/28240605/targeting-ppar%C3%AE-in-the-epigenome-rescues-genetic-metabolic-defects-in-mice
#19
Raymond E Soccio, Zhenghui Li, Eric R Chen, Yee Hoon Foong, Kiara K Benson, Joanna R Dispirito, Shannon E Mullican, Matthew J Emmett, Erika R Briggs, Lindsey C Peed, Richard K Dzeng, Carlos J Medina, Jennifer F Jolivert, Megan Kissig, Satyajit R Rajapurkar, Manashree Damle, Hee-Woong Lim, Kyoung-Jae Won, Patrick Seale, David J Steger, Mitchell A Lazar
Obesity causes insulin resistance, and PPARγ ligands such as rosiglitazone are insulin sensitizing, yet the mechanisms remain unclear. In C57BL/6 (B6) mice, obesity induced by a high-fat diet (HFD) has major effects on visceral epididymal adipose tissue (eWAT). Here, we report that HFD-induced obesity in B6 mice also altered the activity of gene regulatory elements and genome-wide occupancy of PPARγ. Rosiglitazone treatment restored insulin sensitivity in obese B6 mice, yet, surprisingly, had little effect on gene expression in eWAT...
February 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28239649/switching-harmful-visceral-fat-to-beneficial-energy-combustion-improves-metabolic-dysfunctions
#20
Xiaoyan Yang, Wenhai Sui, Meng Zhang, Mei Dong, Sharon Lim, Takahiro Seki, Ziheng Guo, Carina Fischer, Huixia Lu, Cheng Zhang, Jianmin Yang, Meng Zhang, Yangang Wang, Caixia Cao, Yanyan Gao, Xingguo Zhao, Meili Sun, Yuping Sun, Rujie Zhuang, Nilesh J Samani, Yun Zhang, Yihai Cao
Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature-dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake...
February 23, 2017: JCI Insight
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