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Obesity epigenetics

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https://www.readbyqxmd.com/read/28324105/thyroid-hormone-dependent-epigenetic-regulation-of-melanocortin-4-receptor-levels-in-female-offspring-of-obese-rats
#1
T Tabachnik, T Kisliouk, A Marco, N Meiri, A Weller
Maternal obesity is a risk factor for offspring obesity. Melanocortin 4 receptor (Mc4r) is one of the mediators of food intake and energy balance. This study examines epigenetic mechanisms underlying altered Mc4r levels in the hypothalamic paraventricular nucleus in offspring of high-fat diet (HFD)-induced obese dams, and aims to elucidate the role of thyroid hormones in epigenetic regulation and tagging of their nucleosome at the Mc4r promoter. Female Wistar rats were fed HFD or chow from weaning through gestation and lactation...
January 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323978/assisted-reproductive-technologies-predispose-to-insulin-resistance-and-obesity-in-male-mice-challenged-with-a-high-fat-diet
#2
David Cerny, Claudio Sartori, Stefano F Rimoldi, Théo Meister, Rodrigo Soria, Elisa Bouillet, Urs Scherrer, Emrush Rexhaj
ART alters glucose homeostasis in mice and humans, but the underlying mechanisms are incompletely understood. ART induces endothelial dysfunction and arterial hypertension by epigenetic alteration of the eNOS gene. In eNOS deficient mice, insulin resistance is related to impaired insulin stimulation of muscle blood flow and substrate delivery and defective intrinsic skeletal muscle glucose uptake. We, therefore, assessed glucose tolerance, insulin sensitivity (euglycemic clamp), insulin stimulation of muscle blood flow in vivo and muscle glucose uptake in vitro in male ART and control mice fed a normal chow (NC) or challenged with a high fat diet (HFD) during 8 weeks...
February 8, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323958/jmjd3-is-crucial-for-female-avpv-rip-cre-neuron-controlled-kisspeptin-estrogen-feedback-loop-and-reproductive-function
#3
Anying Song, Shujun Jiang, Qinghua Wang, Jianghuan Zou, Zhaoyu Lin, Xiang Gao
The hypothalamic-pituitary-gonadal axis controls development, reproduction, and metabolism. While most studies were focusing on the hierarch from brain to gonad, many questions remain unresolved concerning the feedback from gonad to the central nervous system, especially on the potential epigenetic modification in hypothalamic neurons. In this report, we generated genetically modified mice lacking histone H3 lysine 27 demethylase JMJD3 in hypothalamic RIP-Cre neurons. The female mutant mice display late-onset obesity due to reduced locomotor activity and decreased energy expenditure...
March 9, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320484/nutritional-intervention-preconception-and-during-pregnancy-to-maintain-healthy-glucose-metabolism-and-offspring-health-nipper-study-protocol-for-a-randomised-controlled-trial
#4
Keith M Godfrey, Wayne Cutfield, Shiao-Yng Chan, Philip N Baker, Yap-Seng Chong
BACKGROUND: Improved maternal nutrition and glycaemic control before and during pregnancy are thought to benefit the health of the mother, with consequent benefits for infant body composition and later obesity risk. Maternal insulin resistance and glycaemia around conception and in early pregnancy may be key determinants of maternal physiology and placental function, affecting fetal nutrient supply and maternal-feto-placental communications throughout gestation, with implications for later postnatal health...
March 20, 2017: Trials
https://www.readbyqxmd.com/read/28319137/the-h3k27-demethylase-utx-regulates-adipogenesis-in-a-differentiation-stage-dependent-manner
#5
Kazushige Ota, Kit I Tong, Kouichiro Goto, Shuta Tomida, Akiyoshi Komuro, Zhong Wang, Kazuto Nishio, Hitoshi Okada
Understanding the molecular mechanisms that drive adipogenesis is important in developing new treatments for obesity and diabetes. Epigenetic regulations determine the capacity of adipogenesis. In this study, we examined the role of a histone H3 lysine 27 demethylase, the ubiquitously transcribed tetratricopeptide repeat protein on the X chromosome (Utx), in the differentiation of mouse embryonic stem cells (mESCs) to adipocytes. Using gene trapping, we examined Utx-deficient male mESCs to determine whether loss of Utx would enhance or inhibit the differentiation of mESCs to adipocytes...
2017: PloS One
https://www.readbyqxmd.com/read/28315898/modifiable-risk-factors-and-interventions-for-childhood-obesity-prevention-within-the-first-1-000-days
#6
Anne M Dattilo
Worldwide, the prevalence of childhood obesity has increased, amounting to 42 million overweight or obese children, and there is increasing evidence that the origins are within the first 1,000 days: the period of conception through 2 years. Antecedents of early childhood obesity are multifactorial, and associations of varying strength have been documented for genetic/epigenetic, biologic, dietary, environmental, social, and behavioral influences. Modifiable factors in pregnancy and early infancy associated with childhood obesity include maternal overweight/obesity, maternal smoking, gestational weight gain, infant and young child feeding, caregiver responsive feeding practices, as well as sleep duration, and physical activity...
2017: Nestlé Nutrition Institute Workshop Series
https://www.readbyqxmd.com/read/28291256/exercise-rescues-obese-mothers-insulin-sensitivity-placental-hypoxia-and-male-offspring-insulin-sensitivity
#7
Denise S Fernandez-Twinn, Geraldine Gascoin, Barbara Musial, Sarah Carr, Daniella Duque-Guimaraes, Heather L Blackmore, Maria Z Alfaradhi, Elena Loche, Amanda N Sferruzzi-Perri, Abigail L Fowden, Susan E Ozanne
The prevalence of obesity during pregnancy continues to increase at alarming rates. This is concerning as in addition to immediate impacts on maternal wellbeing, obesity during pregnancy has detrimental effects on the long-term health of the offspring through non-genetic mechanisms. A major knowledge gap limiting our capacity to develop intervention strategies is the lack of understanding of the factors in the obese mother that mediate these epigenetic effects on the offspring. We used a mouse model of maternal-diet induced obesity to define predictive correlations between maternal factors and offspring insulin resistance...
March 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28289477/obesity-accelerates-epigenetic-aging-in-middle-aged-but-not-in-elderly-individuals
#8
Tapio Nevalainen, Laura Kananen, Saara Marttila, Juulia Jylhävä, Nina Mononen, Mika Kähönen, Olli T Raitakari, Antti Hervonen, Marja Jylhä, Terho Lehtimäki, Mikko Hurme
BACKGROUND: Human aging is associated with profound changes in one of the major epigenetic mechanisms, DNA methylation. Some of these changes occur in a clock-like fashion, i.e., correlating with the calendar age of an individual, thus providing a new aging biomarker. Some reports have identified factors associated with the acceleration of the epigenetic age. However, it is also important to analyze the temporal changes in the epigenetic age, i.e., the duration of the observed acceleration, and the effects of the possible therapeutic and lifestyle modifications...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28283671/obesity-energy-balance-and-spermatogenesis
#9
Pedro Fontes Oliveira, Mario Sousa, Branca M Silva, Mariana P Monteiro, Marco G Alves
Obesity has grown to pandemic proportions. It affects an increasing number of children, adolescents and young adults exposed to the silent co-morbidities of this disorder for a longer period. Infertility has arisen as one important comorbidity associated with the energy dysfunction promoted by obesity. Spermatogenesis is a highly regulated process that is determined by specific energetic requirements. The reproductive potential of males relies on hormonal-dependent and independent stimuli that control sperm quality...
March 10, 2017: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/28277977/human-liver-epigenetic-alterations-in-non-alcoholic-steatohepatitis-are-related-to-insulin-action
#10
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/28266632/specific-cpg-hyper-methylation-leads-to-ankrd26-gene-down-regulation-in-white-adipose-tissue-of-a-mouse-model-of-diet-induced-obesity
#11
Gregory A Raciti, Rosa Spinelli, Antonella Desiderio, Michele Longo, Luca Parrillo, Cecilia Nigro, Vittoria D'Esposito, Paola Mirra, Francesca Fiory, Vincenzo Pilone, Pietro Forestieri, Pietro Formisano, Ira Pastan, Claudia Miele, Francesco Beguinot
Epigenetic modifications alter transcriptional activity and contribute to the effects of environment on the individual risk of obesity and Type 2 Diabetes (T2D). Here, we have estimated the in vivo effect of a fat-enriched diet (HFD) on the expression and the epigenetic regulation of the Ankyrin repeat domain 26 (Ankrd26) gene, which is associated with the onset of these disorders. In visceral adipose tissue (VAT), HFD exposure determined a specific hyper-methylation of Ankrd26 promoter at the -436 and -431 bp CpG sites (CpGs) and impaired its expression...
March 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28264723/developmental-pathways-to-adiposity-begin-before-birth-and-are-influenced-by-genotype-prenatal-environment-and-epigenome
#12
Xinyi Lin, Ives Yubin Lim, Yonghui Wu, Ai Ling Teh, Li Chen, Izzuddin M Aris, Shu E Soh, Mya Thway Tint, Julia L MacIsaac, Alexander M Morin, Fabian Yap, Kok Hian Tan, Seang Mei Saw, Michael S Kobor, Michael J Meaney, Keith M Godfrey, Yap Seng Chong, Joanna D Holbrook, Yung Seng Lee, Peter D Gluckman, Neerja Karnani
BACKGROUND: Obesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood...
March 7, 2017: BMC Medicine
https://www.readbyqxmd.com/read/28256005/regulatory-role-of-n-6-methyladenosine-m-6-a-methylation-in-rna-processing-and-human-diseases
#13
Wenqiang Wei, Xinying Ji, Xiangqian Guo, Shaoping Ji
N(6) -methyladenosine (m(6) A) modification is an abundant and conservative RNA modification in bacterial and eukaryotic cells. m(6) A modification mainly occurs in the 3' untranslated regions (UTRs) and near the stop codons of mRNA. Diverse strategies have been developed for identifying m(6) A sites in single nucleotide resolution. Dynamic regulation of m(6) A is found in metabolism, embryogenesis and developmental processes, indicating a possible epigenetic regulation role along RNA processing and exerting biological functions...
March 3, 2017: Journal of Cellular Biochemistry
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
#14
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/28249902/hypercholesterolemia-increases-colorectal-cancer-incidence-by-reducing-production-of-nkt-and-%C3%AE-%C3%AE-t-cells-from-hematopoietic-stem-cells
#15
Guodong Tie, Jinglian Yan, Lyne Khair, Julia Messina, April Deng, Joonsoo Kang, Thomas Fazzio, Louis M Messina
Obesity will soon surpass smoking as the most preventable cause of cancer. Hypercholesterolemia, a common comorbidity of obesity, has been shown to increase cancer risk, especially colorectal cancer. However, the mechanism by which hypercholesterolemia or any metabolic disorder increases cancer risk remains unknown. In this study, we show that hypercholesterolemia increases the incidence and pathological severity of colorectal neoplasia in two independent mouse models. Hypochlosterolemia induced an oxidant-stress dependent increase in miR101c which downregulated Tet1 in hematopoietic stem cells (HSC), resulting in reduced expression of genes critical to natural killer T cell (NKT) and γδ T cell differentiation...
March 1, 2017: Cancer Research
https://www.readbyqxmd.com/read/28242765/novel-role-for-wnt-inhibitor-apcdd1-in-adipocyte-differentiation-implications-for-diet-induced-obesity
#16
Nicole K H Yiew, Tapan K Chatterjee, Yao Liang Tang, Rod Pellenberg, Brian K Stansfield, Zsolt Bagi, David J Fulton, David W Stepp, Weiqin Chen, Vijay Patel, Vinayak M Kamath, Sheldon E Litwin, David Y Hui, Steven M Rudich, Ha Won Kim, Neal L Weintraub
Impaired adipogenic differentiation during diet-induced obesity (DIO) promotes adipocyte hypertrophy and inflammation, thereby contributing to metabolic disease. Adenomatosis polyposis coli downregulated 1 (APCDD1) has recently been identified as an inhibitor of Wnt signaling, a key regulator of adipogenic differentiation. Here, we report a novel role for APCDD1 in adipogenic differentiation via repression of Wnt signaling, and an epigenetic linkage between miR-130 and APCDD1 in DIO. APCDD1 expression was significantly upregulated in mature adipocytes as compared to undifferentiated preadipocytes in both human and mouse subcutaneous adipose tissues...
February 27, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28222718/abnormal-epigenetic-changes-during-differentiation-of-human-skeletal-muscle-stem-cells-from-obese-subjects
#17
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
#18
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
#19
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 17, 2017: Molecular Aspects of Medicine
https://www.readbyqxmd.com/read/28214526/recent-advances-in-human-genetics-and-epigenetics-of-adiposity-pathway-to-precision-medicine
#20
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
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