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Genomics and Obesity

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https://www.readbyqxmd.com/read/29666371/integration-of-human-adipocyte-chromosomal-interactions-with-adipose-gene-expression-prioritizes-obesity-related-genes-from-gwas
#1
David Z Pan, Kristina M Garske, Marcus Alvarez, Yash V Bhagat, James Boocock, Elina Nikkola, Zong Miao, Chelsea K Raulerson, Rita M Cantor, Mete Civelek, Craig A Glastonbury, Kerrin S Small, Michael Boehnke, Aldons J Lusis, Janet S Sinsheimer, Karen L Mohlke, Markku Laakso, Päivi Pajukanta, Arthur Ko
Increased adiposity is a hallmark of obesity and overweight, which affect 2.2 billion people world-wide. Understanding the genetic and molecular mechanisms that underlie obesity-related phenotypes can help to improve treatment options and drug development. Here we perform promoter Capture Hi-C in human adipocytes to investigate interactions between gene promoters and distal elements as a transcription-regulating mechanism contributing to these phenotypes. We find that promoter-interacting elements in human adipocytes are enriched for adipose-related transcription factor motifs, such as PPARG and CEBPB, and contribute to heritability of cis-regulated gene expression...
April 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29663637/reproductive-health-obesity-and-cardiometabolic-risk-factors-among-samoan-women
#2
H Maredia, N L Hawley, G Lambert-Messerlian, U Fidow, M S Reupena, T Naseri, S T McGarvey
OBJECTIVES: Obesity leads to deleterious effects on not only cardiovascular health but also on the reproductive health of women. We estimate the prevalence of menstrual irregularity and of polycystic ovarian syndrome (PCOS) in Samoan women, among whom obesity prevalence is extremely high. We explore the association of these reproductive health conditions with adiposity, cardiometabolic risk factors, and androgen levels. METHODS: A cross-sectional sample of Samoan women 25-39 years of age (n = 470) from a larger population-based genome-wide association study of adiposity and cardiometabolic disease was assessed for the prevalence of oligomenorrhea/amenorrhea (OM/AM) using a self-reported questionnaire...
April 16, 2018: American Journal of Human Biology: the Official Journal of the Human Biology Council
https://www.readbyqxmd.com/read/29659694/nutritional-genomics-and-direct-to-consumer-genetic-testing-an-overview
#3
Marta Guasch-Ferré, Hassan S Dashti, Jordi Merino
The increasing prevalence in polygenic diseases, such as obesity, cardiovascular disease, and type 2 diabetes, observed over the past few decades is more likely linked to a rapid transition in lifestyle rather than to changes in the sequence of the nuclear genome. In the new era of precision medicine, nutritional genomics holds the promise to be translated into tailored nutritional strategies to prevent and manage polygenic diseases more effectively. Nutritional genomics aims to prevent, treat, and manage polygenic diseases through targeted therapies formulated from individuals' genetic makeup and dietary intake...
March 1, 2018: Advances in Nutrition
https://www.readbyqxmd.com/read/29659562/organic-cation-transporter-1-oct1-modulates-multiple-cardiometabolic-traits-through-effects-on-hepatic-thiamine-content
#4
Xiaomin Liang, Sook Wah Yee, Huan-Chieh Chien, Eugene C Chen, Qi Luo, Ling Zou, Meiling Piao, Arias Mifune, Ligong Chen, Meredith E Calvert, Sarah King, Frode Norheim, Janna Abad, Ronald M Krauss, Kathleen M Giacomini
A constellation of metabolic disorders, including obesity, dysregulated lipids, and elevations in blood glucose levels, has been associated with cardiovascular disease and diabetes. Analysis of data from recently published genome-wide association studies (GWAS) demonstrated that reduced-function polymorphisms in the organic cation transporter, OCT1 (SLC22A1), are significantly associated with higher total cholesterol, low-density lipoprotein (LDL) cholesterol, and triglyceride (TG) levels and an increased risk for type 2 diabetes mellitus, yet the mechanism linking OCT1 to these metabolic traits remains puzzling...
April 16, 2018: PLoS Biology
https://www.readbyqxmd.com/read/29652634/emerging-applications-of-genome-editing-technology-to-examine-functionality-of-gwas-associated-variants-for-complex-traits
#5
Andrew J P Smith, Panos Deloukas, Patricia B Munroe
Over the last decade, genome-wide association studies (GWAS) have propelled the discovery of thousands of loci associated with complex diseases. The focus is now turning towards the function of these association signals, determining the causal variant(s) amongst those in strong linkage disequilibrium, and identifying their underlying mechanisms, such as long-range gene regulation. Genome-editing techniques utilising zinc-finger nucleases (ZFN), transcription activator-like effector nucleases (TALENs) and clustered regularly-interspaced short palindromic repeats with Cas9 nuclease (CRISPR-Cas9), are becoming the tools of choice to establish functionality for these variants, due to the ability to assess effects of single variants in vivo...
April 13, 2018: Physiological Genomics
https://www.readbyqxmd.com/read/29643945/epigenome-wide-association-study-of-metabolic-syndrome-in-african-american-adults
#6
Tomi Akinyemiju, Anh N Do, Amit Patki, Stella Aslibekyan, Degui Zhi, Bertha Hidalgo, Hemant K Tiwari, Devin Absher, Xin Geng, Donna K Arnett, Marguerite R Irvin
Background: The high prevalence of obesity among US adults has resulted in significant increases in associated metabolic disorders such as diabetes, dyslipidemia, and high blood pressure. Together, these disorders constitute metabolic syndrome, a clinically defined condition highly prevalent among African-Americans. Identifying epigenetic alterations associated with metabolic syndrome may provide additional information regarding etiology beyond current evidence from genome-wide association studies...
2018: Clinical Epigenetics
https://www.readbyqxmd.com/read/29642370/global-transcriptome-analysis-of-brown-adipose-tissue-of-diet-induced-obese-mice
#7
Jingyi Cao, Qi Zhu, Lin Liu, Bradley J Glazier, Benjamin C Hinkel, Chun Liang, Haifei Shi
Consumption of a high-fat diet (HFD) promotes the development of obesity, a disease resulting from an imbalance between energy intake and energy expenditure. Brown adipose tissue (BAT) has thermogenic capacity that burns calories to produce heat, and it is a potential target for the treatment and prevention of obesity. There is limited information regarding the impact of HFD on the BAT transcriptome. We hypothesized that HFD-induced obesity would lead to transcriptional regulation of BAT genes. RNA sequencing was used to generate global transcriptome profiles from BAT of lean mice fed with a low-fat diet (LFD) and obese mice fed with a HFD...
April 6, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29627041/obesity-and-asthma
#8
REVIEW
Ubong Peters, Anne E Dixon, Erick Forno
Obesity is a vast public health problem and both a major risk factor and disease modifier for asthma in children and adults. Obese subjects have increased asthma risk, and obese asthmatic patients have more symptoms, more frequent and severe exacerbations, reduced response to several asthma medications, and decreased quality of life. Obese asthma is a complex syndrome, including different phenotypes of disease that are just beginning to be understood. We examine the epidemiology and characteristics of this syndrome in children and adults, as well as the changes in lung function seen in each age group...
April 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29626477/chronic-cold-exposure-results-in-subcutaneous-adipose-tissue-browning-and-altered-global-metabolism-in-qinghai-tibetan-plateau-pika-ochotona-curzoniae
#9
Jia Li, Quanyu Yang, Zhenzhong Bai, Gregg L Semenza, Ri-Li Ge
The plateau pika (Ochotona curzoniae), one of the indigenous animals of the Qinghai-Tibet Plateau, is adapted to life in a cold and hypoxic environment. We conducted a series of genomic, proteomic and morphological studies to investigate whether changes in energy metabolism contribute to adaptation of the plateau pika to cold stress by analyzing summer and winter cohorts. The winter group showed strong morphological and histological features of brown adipose tissue (BAT) in subcutaneous white adipose tissue (sWAT)...
April 4, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29626103/role-of-rab5a-in-fshr-mediated-signal-transduction-in-human-granulosa-cells
#10
Kai Zhu, Shang Li, Jiansheng Liu, Yan Hong, Zi-Jiang Chen, Yanzhi Du
Polycystic ovary syndrome, a common condition characterized by endocrine dysfunction, menstrual irregularity, anovulation, and polycystic ovaries, affects 5%-7% of reproductive-age women. RAB5B, which is identified by a genome-wide association study as a risk locus for this syndrome, encodes a small GTPase involved in control of receptor internalization and early endosome fusion. We found that RAB5A mRNA levels in luteinized granulosa cells of obese patients with polycystic ovary syndrome were lower than in those of obese women without the syndrome...
April 6, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29625905/myogenic-oxidative-imbalance-interferes-with-antral-motility-in-obese-subjects
#11
Annunziata Scirocco, Lucia Pallotta, Marco Rengo, Antonia Ignazzi, Marilia Carabotti, Alessia Cicenia, Rosa Vona, Piero Chirletti, Maria Antonietta Maselli, Rossella Donghia, Mariagrazia Coluzzi, Paola Matarrese, Gianfranco Silecchia, Carola Severi
BACKGROUND: Obesity is characterized by a systemic low-grade chronic inflammatory oxidative condition that affects vascular and cardiac smooth muscle relaxation. In human antrum, relaxation is mediated by vasoactive intestinal peptide (VIP) through cAMP and cGMP signaling pathways. A genome-wide association study has demonstrated an association between VIP and obesity. AIM: To evaluate smooth muscle activity in human obese antrum, both in in vitro preparations as well as in vivo...
March 14, 2018: Digestive and Liver Disease
https://www.readbyqxmd.com/read/29625575/targeted-genome-engineering-in-human-induced-pluripotent-stem-cells-from-patients-with-hemophilia-b-using-the-crispr-cas9-system
#12
Cuicui Lyu, Jun Shen, Rui Wang, Haihui Gu, Jianping Zhang, Feng Xue, Xiaofan Liu, Wei Liu, Rongfeng Fu, Liyan Zhang, Huiyuan Li, Xiaobing Zhang, Tao Cheng, Renchi Yang, Lei Zhang
BACKGROUND: Replacement therapy for hemophilia remains a lifelong treatment. Only gene therapy can cure hemophilia at a fundamental level. The clustered regularly interspaced short palindromic repeats-CRISPR associated nuclease 9 (CRISPR-Cas9) system is a versatile and convenient genome editing tool which can be applied to gene therapy for hemophilia. METHODS: A patient's induced pluripotent stem cells (iPSCs) were generated from their peripheral blood mononuclear cells (PBMNCs) using episomal vectors...
April 6, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29608557/a-high-throughput-functional-screen-of-human-body-mass-index-gwas-loci-using-tissue-specific-rnai-drosophila-melanogaster-crosses
#13
Thomas J Baranski, Aldi T Kraja, Jill L Fink, Mary Feitosa, Petra A Lenzini, Ingrid B Borecki, Ching-Ti Liu, L Adrienne Cupples, Kari E North, Michael A Province
Human GWAS of obesity have been successful in identifying loci associated with adiposity, but for the most part, these are non-coding SNPs whose function, or even whose gene of action, is unknown. To help identify the genes on which these human BMI loci may be operating, we conducted a high throughput screen in Drosophila Melanogaster. Starting with 78 BMI loci from two recently published GWAS meta-analyses, we identified fly orthologs of all nearby genes (± 250KB). We crossed RNAi knockdown lines of each gene with flies containing tissue-specific drivers to knock down (KD) the expression of the genes only in the brain and the fat body...
April 2, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29608535/genetic-survey-of-adult-onset-idiopathic-intracranial-hypertension
#14
Markus H Kuehn, Rajashree Mishra, Benjamin E Deonovic, Kimberly N Miller, Shana E McCormack, Grant T Liu, Mark J Kupersmith, Michael Wall
BACKGROUND: Idiopathic intracranial hypertension (IIH) is a condition characterized by increased intracranial pressure of unknown cause. IIH has been shown to be associated with female sex as well as obesity. This genome-wide association study was performed to determine whether genetic variants are associated with this condition. METHODS: We analyzed the chromosomal DNA of 95 patients with IIH enrolled in the Idiopathic Intracranial Hypertension Treatment Trial and 95 controls matched on sex, body mass index, and self-reported ethnicity...
March 30, 2018: Journal of Neuro-ophthalmology: the Official Journal of the North American Neuro-Ophthalmology Society
https://www.readbyqxmd.com/read/29606151/fto-variant-is-not-associated-with-osteoarthritis-in-the-chinese-han-population-replication-study-for-a-genome-wide-association-study-identified-risk-loci
#15
Jin Dai, Pu Ying, Dongquan Shi, Huacheng Hou, Ye Sun, Zhihong Xu, Dongyang Chen, Guoqiang Zhang, Ming Ni, Huajian Teng, Yan Wang, Qing Jiang
BACKGROUND: Osteoarthritis is the most prevalent form of arthritis worldwide and is the major cause of pain and loss of function in elderly people. A signal of the fat mass and obesity-associated (FTO) gene had been reported in a genome-wide association study of osteoarthritis. The FTO polymorphism (rs8044769) might exert its effect on osteoarthritis through obesity, because it was reported as a body mass index-associated single-nucleotide polymorphism. And replication studies showed inconsistent results for this association...
April 2, 2018: Journal of Orthopaedic Surgery and Research
https://www.readbyqxmd.com/read/29605715/a-computational-biology-approach-of-a-genome-wide-screen-connected-mirnas-to-obesity-and-type-2-diabetes
#16
Pascal Gottmann, Meriem Ouni, Sophie Sausenthaler, Julian Roos, Laura Stirm, Markus Jähnert, Anne Kamitz, Nicole Hallahan, Wenke Jonas, Andreas Fritsche, Hans-Ulrich Häring, Harald Staiger, Matthias Blüher, Pamela Fischer-Posovszky, Heike Vogel, Annette Schürmann
OBJECTIVE: Obesity and type 2 diabetes (T2D) arise from the interplay between genetic, epigenetic, and environmental factors. The aim of this study was to combine bioinformatics and functional studies to identify miRNAs that contribute to obesity and T2D. METHODS: A computational framework (miR-QTL-Scan) was applied by combining QTL, miRNA prediction, and transcriptomics in order to enhance the power for the discovery of miRNAs as regulative elements. Expression of several miRNAs was analyzed in human adipose tissue and blood cells and miR-31 was manipulated in a human fat cell line...
March 15, 2018: Molecular Metabolism
https://www.readbyqxmd.com/read/29600520/identification-of-differentially-regulated-deceitful-proteins-in-sh-sy5y-cells-engineered-with-tet-regulated-protein-expression-system
#17
Aylin Kanli, Murat Kasap, Kubra K Yoneten, Gurler Akpinar, Mehmet Dogan Gulkac
Tetracycline regulated protein expression in mammalian cells is a powerful tool to predict the physiological function, cellular localization, and stability of a protein. In addition, to predict metabolic networks affected by the expression of wild-type or mutant forms of proteins, researchers generally produce a single mammalian cell clone that can express the protein of interest under tetracycline control and study the changes occurring in overall proteome before and after expression of a protein of interest...
March 30, 2018: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/29594113/interplay-of-inflammatory-mediators-with-epigenetics-and-cartilage-modifications-in-osteoarthritis
#18
REVIEW
Swarna Raman, Una FitzGerald, J Mary Murphy
Osteoarthritis (OA), a degenerative disease of diarthrodial joints, is influenced by mechanical and inflammatory factors with aging, obesity, chronic injuries, and secondary diseases thought to be major factors driving the process of articular cartilage degeneration. Chondrocytes, the cellular component of cartilage, reside in an avascular environment and normally have limited potential to replicate. However, extrinsic factors such as injury to the joint or intrinsic alterations to the chondrocytes themselves can lead to an altered phenotype and development of OA...
2018: Frontiers in Bioengineering and Biotechnology
https://www.readbyqxmd.com/read/29580070/circadian-gene-methylation-profiles-are-associated-with-obesity-metabolic-disturbances-and-carbohydrate-intake
#19
Omar Ramos-Lopez, Mirian Samblas, Fermin I Milagro, Jose I Riezu-Boj, A B Crujeiras, J Alfredo Martinez, Mena Project
The circadian clock regulates the daily rhythms of several physiological and behavioral processes. Disruptions in clock genes have been associated with obesity and related comorbidities. This study aimed to analyze the association of DNA methylation signatures at circadian rhythm pathway genes with body mass index (BMI), metabolic profiles and dietary intakes. DNA methylation profiling was determined by microarray in white blood cells from 474 adults from the Methyl Epigenome Network Association (MENA) project...
March 26, 2018: Chronobiology International
https://www.readbyqxmd.com/read/29569324/distinct-gene-expression-pathways-in-islets-from-individuals-with-short-and-long-duration-type-1-diabetes
#20
Teresa L Mastracci, Jean-Valery Turatsinze, Benita K Book, Ivan A Restrepo, Michael J Pugia, Eric A Wiebke, Mark D Pescovitz, Decio L Eizirik, Raghavendra G Mirmira
AIMS: Our current understanding of the pathogenesis of type 1 diabetes (T1D) arose in large part from studies using the non-obese diabetic (NOD) mouse model. In the present study, we chose a human-focused method to investigate T1D disease mechanisms and potential targets for therapeutic intervention by directly analyzing human donor pancreatic islets from individuals with T1D. MATERIALS AND METHODS: We obtained islets from a young individual with T1D for three years and an older individual with T1D for 27 years and performed unbiased functional genomic analysis by high-depth RNA sequencing; the T1D islets were compared with islets isolated from three non-diabetic donors...
March 22, 2018: Diabetes, Obesity & Metabolism
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