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Obesity methylation

Gary J Hausman
Adipose tissue exists in many locations or depots that differ from one another based on numerous and various characteristics. The unique "layered" anatomical feature of subcutaneous adipose tissue (SAT) in man and the pig is reviewed and discussed. The origin of fetal pig adipose tissue subcutaneous layers is reviewed before the onset of adipogenesis and after the overt adipogenesis. Furthermore, the distinguishing characteristics of developing outer SAT layer (OSQ) and middle SAT layer (MSQ) in pigs are reviewed...
March 16, 2018: Hormone Molecular Biology and Clinical Investigation
Giuseppa Patti, Marta Giaccardi, Valeria Capra, Flavia Napoli, Giuliana Cangemi, Sara Notarnicola, Sara Guzzetti, Silvia Russo, Mohamad Maghnie, Natascia Di Iorgi
Context: There is little information on long-term natural history of Silver-Russell syndrome (SRS). Objective: To describe the phenotypes and the metabolic status in adults with SRS. Design: Clinical and metabolic evaluations in adults with a molecular diagnosis of SRS. Partecipants: 7Caucasian patients (aged 18 to 46 years, mean age 26.9 years) were studied. Two had chromosome 7 maternal uniparental disomy, 3 had 11p15 loss of methylation and 2 had 11p15 duplication...
March 13, 2018: Journal of Clinical Endocrinology and Metabolism
Omar Ramos-Lopez, Mirian Samblas, Fermin I Milagro, M Angeles Zulet, Maria L Mansego, Jose I Riezu-Boj, J Alfredo Martinez
Folate deficiency has been putatively implicated in the onset of diverse metabolic abnormalities, including insulin resistance, by altering epigenetic processes on key regulatory genes. The calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) is involved in the regulation of critical metabolic processes such as adiposity and glucose homeostasis. This study hypothesized associations between low folate intakes and lower methylation levels of the CAMKK2 gene, with the presence of metabolic alterations in subjects with obesity...
February 2018: Nutrition Research
Meghan McGee, Shannon Bainbridge, Bénédicte Fontaine-Bisson
The fetal origins of health and disease framework has identified extremes in fetal growth and birth weight as factors associated with the lifelong generation of chronic diseases such as obesity, diabetes, cardiovascular disease, and hypertension. Maternal nutrition plays a critical role in fetal and placental development, in part by providing the methyl groups required to establish the fetus's genome structure and function, notably through DNA methylation. The goal of this narrative review is to describe the role of maternal dietary methyl donor (methionine, folate, and choline) and cofactor (zinc and vitamins B2, B6, and B12) intake in one-carbon metabolism and DNA methylation in the fetus and placenta, as well as their impacts on fetal growth and lifelong health outcomes, with specific examples in animals and humans...
February 26, 2018: Nutrition Reviews
S-S Dong, Y-J Zhang, Y-X Chen, S Yao, R-H Hao, Y Rong, H-M Niu, J-B Chen, Y Guo, T-L Yang
We aimed to summarize the results of genetic association studies for obesity and provide a comprehensive annotation of all susceptibility single nucleotide polymorphisms (SNPs). A total of 72 studies were summarized, resulting in 90,361 susceptibility SNPs (738 index SNPs and 89,623 linkage disequilibrium SNPs). Over 90% of the susceptibility SNPs are located in non-coding regions, and it is challenging to understand their functional significance. Therefore, we annotated these SNPs by using various functional databases...
March 12, 2018: Obesity Reviews: An Official Journal of the International Association for the Study of Obesity
Haiqiang Yao, Shanlan Mo, Ji Wang, Yingshuai Li, Chong-Zhi Wang, Jin-Yi Wan, Zengliang Zhang, Yu Chen, Ranran Sun, Chun-Su Yuan, Xin Liu, Lingru Li, Qi Wang
BACKGROUND/AIMS: Metabolic diseases are leading health concerns in today's global society. In traditional Chinese medicine (TCM), one body type studied is the phlegm-dampness constitution (PC), which predisposes individuals to complex metabolic disorders. Genomic studies have revealed the potential metabolic disorders and the molecular features of PC. The role of epigenetics in the regulation of PC, however, is unknown. METHODS: We analyzed a genome-wide DNA methylation in 12 volunteers using Illumina Infinium Human Methylation450 BeadChip on peripheral blood mononuclear cells (PBMCs)...
March 2, 2018: Cellular Physiology and Biochemistry
Emil Andersen, Lars Roed Ingerslev, Odile Fabre, Ida Donkin, Ali Altıntaş, Soetkin Versteyhe, Thue Bisgaard, Viggo B Kristiansen, David Simar, Romain Barrès
BACKGROUND: Deterioration of the adipogenic potential of preadipocytes may contribute to adipose tissue dysfunction in obesity and type 2 diabetes (T2D). Here, we hypothesized that extracellular factors in obesity epigenetically reprogram adipogenesis potential and metabolic function of preadipocytes. METHODS: The transcriptomic profile of visceral adipose tissue preadipocytes collected from Lean, Obese and Obese with T2D was assessed throughout in vitro differentiation using RNA sequencing...
February 20, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Habib Mosbah, Hassiba Chahdoura, Jannet Kammoun, Malek Besbes Hlila, Hanen Louati, Saoussen Hammami, Guido Flamini, Lotfi Achour, Boulbaba Selmi
BACKGROUND: α-glucosidase is a therapeutic target for diabetes mellitus (DM) and α-glucosidase inhibitors play a vital role in the treatments for the disease. Furthermore, xanthine oxidase (XO) is a key enzyme that catalyzes hypoxanthine and xanthine to uric acid which at high levels can lead to hyperuricemia which is an important cause of gout. Pancreatic lipase (PL) secreted into the duodenum plays a key role in the digestion and absorption of fats. For its importance in lipid digestion, PL represents an attractive target for obesity prevention...
March 5, 2018: BMC Complementary and Alternative Medicine
Cajsa Davegårdh, Sonia García-Calzón, Karl Bacos, Charlotte Ling
BACKGROUND: Type 2 diabetes (T2D) is a multifactorial, polygenic disease caused by impaired insulin secretion and insulin resistance. Genome-wide association studies (GWAS) were expected to resolve a large part of the genetic component of diabetes; yet, the single nucleotide polymorphisms identified by GWAS explain less than 20% of the estimated heritability for T2D. There was subsequently a need to look elsewhere to find disease-causing factors. Mechanisms mediating the interaction between environmental factors and the genome, such as epigenetics, may be of particular importance in the pathogenesis of T2D...
February 7, 2018: Molecular Metabolism
J A Gill, Michele A La Merrill
Metabolic disease is a leading cause of death worldwide, and obesity, a central risk factor, is reaching epidemic proportions. Energy expenditure and brown adipose tissue (BAT) thermogenesis are implicated in metabolic disease, and it is becoming evident that impaired BAT activity is regulated by gene/environment interactions. Peroxisome proliferator-activated receptor γ coactivator 1α (Pgc-1α) is a critical regulator of BAT thermogenesis, which is highly inducible by environmental stimuli such as cold and diet...
May 2017: Environmental Epigenetics
Xinxia Wang, Baofa Sun, Qin Jiang, Ruifan Wu, Min Cai, Yongxi Yao, Qing Liu, Hailing Shi, Jie Feng, Yizhen Wang
BACKGROUND/OBJECTIVE: N6 -methyladenosine (m6 A) modification of mRNA plays an important role in regulating adipogenesis. However, its underlying mechanism remains largely unknown. SUBJECTS/METHODS: Using Jinhua and Landrace pigs as fat and lean models, we presented a comprehensive transcriptome-wide m6 A profiling in adipose tissues from these two pig breeds. Two differentially methylated genes were selected to explore the mechanisms of m6 A-mediated regulation of gene function...
February 27, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Aimo Kannt, Sridharan Rajagopal, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Srinivasan Swaminathan, Mahanandeesha Siddappa Hallur, Rajendra Kristam, Ralf Elvert, Jörg Czech, Anja Pfenninger, Christine Rudolph, Herman Schreuder, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Swarnakumari Birudukota, Shama Shaik, Bharat Ravindra Zope, Raghunadha Reddy Burri, Niranjan Naranapura Anand, Manish Kumar Thakur, Manvi Singh, Reejuana Parveen, Saravanan Kandan, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Sven Ruf, Saravanakumar Dhakshinamoorthy
Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that catalyzes the transfer of a methyl group from the co-factor S-adenosyl-L-methionine (SAM) onto the substrate, nicotinamide (NA) to form 1-methyl-nicotinamide (MNA). Higher NNMT expression and MNA concentrations have been associated with obesity and type-2 diabetes. Here we report a small molecule analog of NA, JBSNF-000088, that inhibits NNMT activity, reduces MNA levels and drives insulin sensitization, glucose modulation and body weight reduction in animal models of metabolic disease...
February 26, 2018: Scientific Reports
Michael K Skinner, Millissia Ben Maamar, Ingrid Sadler-Riggleman, Daniel Beck, Eric Nilsson, Margaux McBirney, Rachel Klukovich, Yeming Xie, Chong Tang, Wei Yan
BACKGROUND: Environmental toxicants such as DDT have been shown to induce the epigenetic transgenerational inheritance of disease (e.g., obesity) through the germline. The current study was designed to investigate the DDT-induced concurrent alterations of a number of different epigenetic processes including DNA methylation, non-coding RNA (ncRNA) and histone retention in sperm. METHODS: Gestating females were exposed transiently to DDT during fetal gonadal development, and then, the directly exposed F1 generation, the directly exposed germline F2 generation and the transgenerational F3 generation sperm were investigated...
February 27, 2018: Epigenetics & Chromatin
Jacqueline Alexander, April M Teague, Jing Chen, Christopher E Aston, Yuet-Kin Leung, Steven Chernausek, Rebecca A Simmons, Sara E Pinney
AIMS/HYPOTHESIS: We hypothesized that diabetes during pregnancy (DDP) alters genome-wide DNA methylation in placenta resulting in differentially methylated loci of metabolically relevant genes and downstream changes in RNA and protein expression. METHODS: We mapped genome-wide DNA methylation with the Infinium 450K Human Methylation Bead Chip in term fetal placentae from Native American and Hispanic women with DDP using a nested case-control design (n = 17 pairs)...
2018: PloS One
Francisco Barajas-Olmos, Federico Centeno-Cruz, Carlos Zerrweck, Iván Imaz-Rosshandler, Angélica Martínez-Hernández, Emilio J Cordova, Claudia Rangel-Escareño, Faustino Gálvez, Armando Castillo, Hernán Maydón, Francisco Campos, Diana Gabriela Maldonado-Pintado, Lorena Orozco
BACKGROUND: Obesity is a well-recognized risk factor for insulin resistance and type 2 diabetes (T2D), although the precise mechanisms underlying the relationship remain unknown. In this study we identified alterations of DNA methylation influencing T2D pathogenesis, in subcutaneous and visceral adipose tissues, liver, and blood from individuals with obesity. METHODS: The study included individuals with obesity, with and without T2D. From these patients, we obtained samples of liver tissue (n = 16), visceral and subcutaneous adipose tissues (n = 30), and peripheral blood (n = 38)...
February 21, 2018: BMC Medical Genetics
I V Yang, W Zhang, E J Davidson, T E Fingerlin, K Kechris, D Dabelea
AIMS: To identify gestational diabetes mellitus exposure-associated DNA methylation changes and assess whether such changes are also associated with adiposity-related outcomes. METHODS: We performed an epigenome-wide association analysis, using Illumina 450k methylation arrays, on whole blood collected, on average, at 10.5 years of age from 81 gestational diabetes-exposed and 81 unexposed offspring enrolled in the EPOCH (Exploring Perinatal Outcomes in Children) study, and on the cord blood of 31 gestational diabetes-exposed and 64 unexposed offspring enrolled in our own 'Healthy Start' cohort...
February 20, 2018: Diabetic Medicine: a Journal of the British Diabetic Association
Madeline Rose Keleher, Rabab Zaidi, Shyam Shah, M Elsa Oakley, Cassondra Pavlatos, Samir El Idrissi, Xiaoyun Xing, Daofeng Li, Ting Wang, James M Cheverud
We investigated maternal obesity in inbred SM/J mice by assigning females to a high-fat diet or a low-fat diet at weaning, mating them to low-fat-fed males, cross-fostering the offspring to low-fat-fed SM/J nurses at birth, and weaning the offspring onto a high-fat or low-fat diet. A maternal high-fat diet exacerbated obesity in the high-fat-fed daughters, causing them to weigh more, have more fat, and have higher serum levels of leptin as adults, accompanied by dozens of gene expression changes and thousands of DNA methylation changes in their livers and hearts...
2018: PloS One
Weina Cao, Yatao Xu, Dan Luo, Muhammad Saeed, Chao Sun
BACKGROUND/AIMS: Impaired adipogenesis may be the underlying cause in the development of obesity and type II diabetes. Mechanistically, the family of Homeobox transcription factors is implicated in the regulation of adipocyte fate. Hoxa5 is highly expressed in adipocytes, and its mRNA expression is decreased during differentiation. However, the function of Hoxa5 in adipose tissue has been poorly understood. The aim of this study is to unveil the role of Hoxa5 on adipocyte differentiation and its underlying mechanisms...
February 7, 2018: Cellular Physiology and Biochemistry
Xunmei Yuan, Kazutaka Tsujimoto, Koshi Hashimoto, Kenichi Kawahori, Nozomi Hanzawa, Miho Hamaguchi, Takami Seki, Makiko Nawa, Tatsuya Ehara, Yohei Kitamura, Izuho Hatada, Morichika Konishi, Nobuyuki Itoh, Yoshimi Nakagawa, Hitoshi Shimano, Takako Takai-Igarashi, Yasutomi Kamei, Yoshihiro Ogawa
The nutritional environment to which animals are exposed in early life can lead to epigenetic changes in the genome that influence the risk of obesity in later life. Here, we demonstrate that the fibroblast growth factor-21 gene (Fgf21) is subject to peroxisome proliferator-activated receptor (PPAR) α-dependent DNA demethylation in the liver during the postnatal period. Reductions in Fgf21 methylation can be enhanced via pharmacologic activation of PPARα during the suckling period. We also reveal that the DNA methylation status of Fgf21, once established in early life, is relatively stable and persists into adulthood...
February 12, 2018: Nature Communications
Sven Ruf, Mahanandeesha Siddappa Hallur, Nisha K Anchan, Indu N Swamy, Karthikai Raj Murugesan, Sayantani Sarkar, Lokesh Kananti Narasimhulu, V P Rama Kishore Putta, Shama Shaik, Devaraj Venkatapura Chandrasekar, Vishal Subhash Mane, Sanjay Venkatachalapathi Kadnur, Juluri Suresh, Ravi Kanth Bhamidipati, Manvi Singh, Raghunadha Reddy Burri, Rajendra Kristam, Herman Schreuder, Joerg Czech, Christine Rudolph, Alexander Marker, Thomas Langer, Ramesh Mullangi, Takeshi Yura, Ramachandraiah Gosu, Aimo Kannt, Saravanakumar Dhakshinamoorthy, Sridharan Rajagopal
Nicotinamide N-methyltransferase (NNMT) has been linked to obesity and diabetes. We have identified a novel nicotinamide (NA) analog, compound 12 that inhibited NNMT enzymatic activity and reduced the formation of 1-methyl-nicotinamide (MNA), the primary metabolite of NA by ∼80% at 2 h when dosed in mice orally at 50 mg/kg.
January 31, 2018: Bioorganic & Medicinal Chemistry Letters
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