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Epigenetics obesity

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https://www.readbyqxmd.com/read/28453643/early-onset-obesity-unrecognized-first-evidence-for-gnas-mutations-and-methylation-changes
#1
Annette Grüters-Kieslich, Monica Reyes, Amita Sharma, Cem Demirci, Terry J DeClue, Erwin Lankes, Dov Tiosano, Dirk Schnabel, Harald Jüppner
Context: Early-onset obesity, characteristic for disorders affecting the leptin-melanocortin pathway, is also observed in pseudohypoparathyroidism type Ia (PHP1A), a disorder caused by maternal GNAS mutations that disrupt expression or function of the stimulatory G protein (Gsα). Mutations and/or epigenetic abnormalities at the same genetic locus are also the cause of pseudohypoparathyroidism type Ib (PHP1B). However, although equivalent biochemical and radiographic findings can be encountered in these related disorders caused by GNAS abnormalities they are considered distinct clinical entities...
April 27, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28453518/lc-ms-ms-quantitative-analysis-reveals-the-association-between-fto-and-dna-methylation
#2
Yuting Zhu, Guangyu Zhou, Xuebin Yu, Qiang Xu, Kai Wang, Dan Xie, Qingkai Yang, Lina Wang
Fat mass and obesity-associated protein (FTO) is α-ketoglutarate-dependent dioxygenase and responsible for demethylating N6-methyladenosine (m6A) in mRNA, 3-methylthymine (m3T) in single-stranded DNA (ssDNA) and 3-methyluracil (m3U) in single-stranded RNA (ssRNA). Its other function remains unknown but thousands of mammalian DNA show 5-methyl-2'-deoxycytidine (5mdC) modification and 5mdC demethylases are required for mammalian energy homeostasis and fertility. Here, we aimed to confirm whether FTO proteins can demethylate 5mdC in DNA...
2017: PloS One
https://www.readbyqxmd.com/read/28448277/long-term-consequences-of-obesity-on-female-fertility-and-the-health-of-the-offspring
#3
Suchitra Chandrasekaran, Genevieve Neal-Perry
PURPOSE OF REVIEW: Obesity has reached near epidemic levels among reproductive age women with a myriad of consequences. Obesity adversely affects the maternal milieu by creating conditions that decrease fertility and increase the risk of gestational diabetes, hypertensive disease in pregnancy, fetal growth abnormalities and congenital anomalies. The effects of obesity are not limited to pregnancy. Indeed, beyond the immediate postpartum period, obese women maintain a higher prevalence of insulin resistance and cardiovascular disease...
April 26, 2017: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/28438343/developmental-and-transmittable-origins-of-obesity-associated-health-disorders
#4
REVIEW
Arin K Oestreich, Kelle H Moley
The current global obesity pandemic is clearly linked to both the increasing prevalence of, and preference for, foods high in calories, specifically fat and sucrose, and declining levels of daily physical activity. A less commonly discussed possible explanation is that risk of obesity begins in utero as a result of developmental plasticity during early life. This idea fits into the broader Developmental Origins of Health and Diseases (DOHAD) hypothesis, which holds that stressful in utero exposure manifests as disease in adulthood...
April 21, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28425976/prenatal-exposure-to-a-maternal-high-fat-diet-affects-histone-modification-of-cardiometabolic-genes-in-newborn-rats
#5
Bijaya Upadhyaya, Tricia Larsen, Shivon Barwari, Eli J Louwagie, Michelle L Baack, Moul Dey
Infants born to women with diabetes or obesity are exposed to excess circulating fuels during fetal heart development and are at higher risk of cardiac diseases. We have previously shown that late-gestation diabetes, especially in conjunction with a maternal high-fat (HF) diet, impairs cardiac functions in rat-offspring. This study investigated changes in genome-wide histone modifications in newborn hearts from rat-pups exposed to maternal diabetes and HF-diet. Chromatin-immunoprecipitation-sequencing revealed a differential peak distribution on gene promoters in exposed pups with respect to acetylation of lysines 9 and 14 and to trimethylation of lysines 4 and 27 in histone H3 (all, false discovery rate, FDR < 0...
April 20, 2017: Nutrients
https://www.readbyqxmd.com/read/28423509/histone-lysine-methyltransferase-g9a-is-a-novel-epigenetic-target-for-the-treatment-of-hepatocellular-carcinoma
#6
Masayuki Yokoyama, Tetsuhiro Chiba, Yoh Zen, Motohiko Oshima, Yuko Kusakabe, Yoshiko Noguchi, Kaori Yuki, Shuhei Koide, Shiro Tara, Atsunori Saraya, Kazumasa Aoyama, Naoya Mimura, Satoru Miyagi, Masanori Inoue, Toru Wakamatsu, Tomoko Saito, Sadahisa Ogasawara, Eiichiro Suzuki, Yoshihiko Ooka, Akinobu Tawada, Masayuki Otsuka, Masaru Miyazaki, Osamu Yokosuka, Atsushi Iwama
Histone H3 lysine 9 dimethylation (H3K9me2) is mainly regulated by the histone lysine methyltransferase G9a and is associated with the repression of transcription. However, both the role of G9a and the significance of H3K9me2 in hepatocellular carcinoma (HCC) cells remain unclear. In this study, we conducted loss-of-function assay of G9a using short-hairpin RNA and pharmacological interference. Knockdown of G9a reduced H3K9me2 levels and impaired both HCC cell growth and sphere formation. However, transforming growth factor β1-induced epithelial mesenchymal transition (EMT) was not suppressed by G9a knockdown...
March 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28416947/dna-methylation-profiles-of-blood-cells-are-distinct-between-early-onset-obese-and-control-individuals
#7
Je-Keun Rhee, Jin-Hee Lee, Hae Kyung Yang, Tae-Min Kim, Kun-Ho Yoon
Obesity is a highly prevalent, chronic disorder that has been increasing in incidence in young patients. Both epigenetic and genetic aberrations may play a role in the pathogenesis of obesity. Therefore, in-depth epigenomic and genomic analyses will advance our understanding of the detailed molecular mechanisms underlying obesity and aid in the selection of potential biomarkers for obesity in youth. Here, we performed microarray-based DNA methylation and gene expression profiling of peripheral white blood cells obtained from six young, obese individuals and six healthy controls...
March 2017: Genomics & Informatics
https://www.readbyqxmd.com/read/28416029/the-health-outcomes-of-human-offspring-conceived-by-assisted-reproductive-technologies-art
#8
M Chen, L K Heilbronn
Concerns have been raised about the health and development of children conceived by assisted reproductive technologies (ART) since 1978. Controversially, ART has been linked with adverse obstetric and perinatal outcomes, an increased risk of birth defects, cancers, and growth and development disorders. Emerging evidence suggests that ART treatment may also predispose individuals to an increased risk of chronic ageing related diseases such as obesity, type 2 diabetes and cardiovascular disease. This review will summarize the available evidence on the short-term and long-term health outcomes of ART singletons, as multiple pregnancies after multiple embryos transfer, are associated with low birth weight and preterm delivery, which can separately increase risk of adverse postnatal outcomes, and impact long-term health...
April 18, 2017: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/28414763/enhanced-offspring-predisposition-to-steatohepatitis-with-maternal-high-fat-diet-is-associated-with-epigenetic-and-microbiome-alterations
#9
Umesh D Wankhade, Ying Zhong, Ping Kang, Maria Alfaro, Sree V Chintapalli, Keshari M Thakali, Kartik Shankar
OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) is an important co-morbidity associated with obesity and a precursor to steatohepatitis. However, the contributions of gestational and early life influences on development of NAFLD and NASH remain poorly appreciated. METHODS: Two independent studies were performed to examine whether maternal over-nutrition via exposure to high fat diet (HFD) leads to exacerbated hepatic responses to post-natal HFD and methionine choline deficient (MCD) diets in the offspring...
2017: PloS One
https://www.readbyqxmd.com/read/28414326/mesenchymal-stem-cells-in-obesity-insights-for-translational-applications
#10
Kenichi Matsushita, Victor J Dzau
Obesity is now a major public health problem worldwide. Lifestyle modification to reduce the characteristic excess body adiposity is important in the treatment of obesity, but effective therapeutic intervention is still needed to control what has become an obesity epidemic. Unfortunately, many anti-obesity drugs have been withdrawn from market due to adverse side effects. Bariatric surgery therefore remains the most effective therapy for severe cases, although such surgery is invasive and researchers continue to seek new control strategies for obesity...
April 17, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28410138/clinical-functional-behavioural-and-epigenomic-biomarkers-of-obesity
#11
Claudio L Lafortuna, Armando R Tovar, Fabio Rastelli, Sarah A Tabozzi, Martina Caramenti, Ximena Orozco-Ruiz, Miriam Aguilar-Lopez, Martha Guevara-Cruz, Azalia Avila-Nava, Nimbe Torres, Gloria Bertoli
Overweight and obesity are highly prevalent conditions worldwide, linked to an increased risk for death, disability and disease due to metabolic and biochemical abnormalities affecting the biological human system throughout different domains. Biomarkers, defined as indicators of biological processes in health and disease, relevant for body mass excess management have been identified according to different criteria, including anthropometric and molecular indexes, as well as physiological and behavioural aspects...
June 1, 2017: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28398573/skeletal-muscle-pgc1%C3%AE-1-nucleosome-position-and-260nt-dna-methylation-determine-exercise-response-and-prevent-ectopic-lipid-accumulation-in-men
#12
Sudip Bajpeyi, Jeffrey D Covington, Erin M Taylor, Laura K Stewart, Jose E Galgani, Tara M Henagan
Endurance exercise has been shown to improve lipid oxidation and increase mitochondrial content in skeletal muscle: two features that have shown dependence on increased expression of the PPAR gamma co-activator 1 alpha (PGC1α). It is also hypothesized that exercise related alterations in PGC1α expression occur through epigenetic regulation of nucleosome positioning in association with differential DNA methylation status within the PCG1α promoter. Here we show that when primary human myotubes from obese, type 2 diabetics are exposed to lipolytic stimulus (PFI) in vitro, nucleosome occupancy surrounding the -260 nucleotide (nt) region, a known regulatory DNA methylation site, is reduced...
April 10, 2017: Endocrinology
https://www.readbyqxmd.com/read/28387357/genome-wide-methylation-analysis-identifies-specific-epigenetic-marks-in-severely-obese-children
#13
Delphine Fradin, Pierre-Yves Boëlle, Marie-Pierre Belot, Fanny Lachaux, Jorg Tost, Céline Besse, Jean-François Deleuze, Gianpaolo De Filippo, Pierre Bougnères
Obesity is a heterogeneous disease with many different subtypes. Epigenetics could contribute to these differences. The aim of this study was to investigate genome-wide DNA methylation searching for methylation marks associated with obesity in children and adolescents. We studied DNA methylation profiles in whole blood cells from 40 obese children and controls using Illumina Infinium HumanMethylation450 BeadChips. After correction for cell heterogeneity and multiple tests, we found that compared to lean controls, 31 CpGs are differentially methylated in obese patients...
April 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28386478/changes-in-the-microrna-profile-observed-in-the-subcutaneous-adipose-tissue-of-obese-patients-after-laparoscopic-adjustable-gastric-banding
#14
Carmela Nardelli, Laura Iaffaldano, Vincenzo Pilone, Giuseppe Labruna, Maddalena Ferrigno, Nicola Carlomagno, Concetta Anna Dodaro, Pietro Forestieri, Pasqualina Buono, Francesco Salvatore, Lucia Sacchetti
Background. Laparoscopic adjustable gastric banding (LAGB) results in significant lasting weight loss and improved metabolism in obese patients. To evaluate whether epigenetic factors could concur to these benefits, we investigated the subcutaneous adipose tissue (SAT) microRNA (miRNA) profile before (T0) and three years (T1) after LAGB in three morbidly obese women. Case Reports. SAT miRNA profiling, evaluated by TaqMan Array, showed four downexpressed (miR-519d, miR-299-5p, miR-212, and miR-671-3p) and two upexpressed (miR-370 and miR-487a) miRNAs at T1 versus T0...
2017: Journal of Obesity
https://www.readbyqxmd.com/read/28386383/genome-wide-hepatic-dna-methylation-changes-in-high-fat-diet-induced-obese-mice
#15
AhRam Yoon, Stephanie A Tammen, Soyoung Park, Sung Nim Han, Sang-Woon Choi
BACKGROUND/OBJECTIVES: A high-fat diet (HFD) induces obesity, which is a major risk factor for cardiovascular disease and cancer, while a calorie-restricted diet can extend life span by reducing the risk of these diseases. It is known that health effects of diet are partially conveyed through epigenetic mechanism including DNA methylation. In this study, we investigated the genome-wide hepatic DNA methylation to identify the epigenetic effects of HFD-induced obesity. MATERIALS AND METHODS: Seven-week-old male C57BL/6 mice were fed control diet (CD), calorie-restricted control diet (CRCD), or HFD for 16 weeks (after one week of acclimation to the control diet)...
April 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28377872/dna-methylation-alters-transcriptional-rates-of-differentially-expressed-genes-and-contributes-to-pathophysiology-in-mice-fed-a-high-fat-diet
#16
Pili Zhang, Tianjiao Chu, N Dedousis, Benjamin S Mantell, Ian Sipula, Lucy Li, Kimberly D Bunce, Patricia A Shaw, Liora S Katz, Jun Zhu, Carmen Argmann, Robert M O'Doherty, David G Peters, Donald K Scott
OBJECTIVE: Overnutrition can alter gene expression patterns through epigenetic mechanisms that may persist through generations. However, it is less clear if overnutrition, for example a high fat diet, modifies epigenetic control of gene expression in adults, or by what molecular mechanisms, or if such mechanisms contribute to the pathology of the metabolic syndrome. Here we test the hypothesis that a high fat diet alters hepatic DNA methylation, transcription and gene expression patterns, and explore the contribution of such changes to the pathophysiology of obesity...
April 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28373182/energy-balance-modulation-impacts-epigenetic-reprogramming-er%C3%AE-and-er%C3%AE-expression-and-mammary-tumor-development-in-mmtv-neu-transgenic-mice
#17
Emily L Rossi, Sarah M Dunlap, Laura W Bowers, Subreen A Khatib, Steven S Doerstling, Laura A Smith, Manu A Sharma, Darcy Holley, Powel H Brown, Marcos R Estecio, Donna F Kusewitt, Linda A deGraffenried, Scott J Bultman, Stephen D Hursting
The association between obesity and breast cancer risk and prognosis is well established in ER-positive disease but less clear in HER2-positive disease. Here, we report preclinical evidence suggesting weight maintenance through calorie restriction may limit risk of HER2-positive breast cancer. In female MMTV-HER2/neu transgenic mice, we found that ERα and ERβ expression, mammary tumorigenesis and survival are energy balance-dependent in association with epigenetic reprogramming. Mice were randomized to receive a calorie restriction (CR), overweight (OW)-inducing, or diet-induced obesity (DIO) regimen (n = 27/group)...
April 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28370258/polyphenic-trait-promotes-liver-cancer-in-a-model-of-epigenetic-instability
#18
Marco Cassano, Sandra Offner, Evarist Planet, Alessandra Piersigilli, Suk Min Jang, Hugues Henry, Markus B Geuking, Catherine Mooser, Kathy D McCoy, Andrew J Macpherson, Didier Trono
Hepatocellular carcinoma (HCC) represents the fifth most common form of cancer worldwide and carries a high mortality rate due to lack of effective treatment. Males are eight times more likely to develop HCC than females, an effect largely driven by sex hormones, albeit through still poorly understood mechanisms. We previously identified TRIM28 (tripartite protein 28), a scaffold protein capable of recruiting a number of chromatin modifiers, as a crucial mediator of sexual dimorphism in the liver. Trim28(hep-/-) mice display sex-specific transcriptional deregulation of a wide range of bile and steroid metabolism genes and development of liver adenomas in males...
March 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28366411/obesity-male-infertility-and-the-sperm-epigenome
#19
REVIEW
James R Craig, Timothy G Jenkins, Douglas T Carrell, James M Hotaling
Obesity is a growing epidemic and a common problem among reproductive-age men that can both cause and exacerbate male-factor infertility by means of endocrine abnormalities, associated comorbidities, and direct effects on the fidelity and throughput of spermatogenesis. Robust epidemiologic, clinical, genetic, epigenetic, and nonhuman animal data support these findings. Recent works in the burgeoning field of epigenetics has demonstrated that paternal obesity can affect offspring metabolic and reproductive phenotypes by means of epigenetic reprogramming of spermatogonial stem cells...
April 2017: Fertility and Sterility
https://www.readbyqxmd.com/read/28366410/introduction-obesity-and-reproduction
#20
David R Meldrum
Women bear the predominant burden of our obesogenic environment, with a higher incidence of obesity than men, more impact on their fertility and success with treatment, and significant maternal and perinatal morbidity and mortality. In this series, the causes, consequences, and solutions regarding the obesity pandemic, the mechanisms of the effect of obesity on the female and male, the epigenetic consequences of male obesity, the marked effects on perinatal outcomes, and the effects of weight loss before conception and during pregnancy are explored...
April 2017: Fertility and Sterility
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