Peisong Sun, Yan Shen, Tian Wang, Ya He, Ye Zhang, Wei Tian, Binkai Yang, Yuanjing Hu
BACKGROUND: The diagnosis of Lynch syndrome-associated endometrial cancer patients is significant for early warning of their relatives. The purpose of this study was to provide diagnostic indicators of Lynch syndrome-associated endometrial cancer by screening the differential clinical and genetic characteristics. METHODS: Clinical information and hysterectomy specimens were collected from 377 eligible patients with endometrial cancer. The MLH1 methylation level was detected by an EZ DNA Methylation-Gold Kit...
May 14, 2021: Cancer Epidemiology
Yufei Lan, Boyang Liu, Hongbo Guo
N 6 -methyladenosine (m6 A) is the most abundant modification in eukaryotic cells, and it regulates RNA transcription, processing, splicing, degradation, and translation. Long non-coding RNAs (lncRNAs), as transcriptional products with no or limited protein coding ability more than 200 nt in length, play an important role in epigenetic modification, mRNA transcription, splicing, stability, translation, and other biological functions. Extensive studies have shown that both m6 A modification and lncRNAs are involved in the pathogenesis of various diseases, such as kinds of cancers, heart failure, Alzheimer's disease, periodontitis, human abdominal aortic aneurysm, and obesity...
June 4, 2021: Molecular Therapy. Nucleic Acids
Longfei Ma, Yangyuxin Huang, Fengjiang Zhang, Dave Schwinn Gao, Na Sun, Jinxuan Ren, Suyun Xia, Jia Li, Xinyi Peng, Lina Yu, Bao-Chun Jiang, Min Yan
Nerve injury-induced gene expression change in the spinal cord is critical for neuropathic pain genesis. RNA N6 -methyladenosine (m6 A) modification represents an additional layer of gene regulation. We showed that spinal nerve ligation (SNL) upregulated the expression of matrix metallopeptidase 24 (MMP24) protein, but not Mmp24 mRNA, in the spinal cord neurons. Blocking the SNL-induced upregulation of spinal MMP24 attenuated local neuron sensitization, neuropathic pain development and maintenance. Conversely, mimicking MMP24 increase promoted the spinal ERK activation and produced evoked nociceptive hypersensitivity...
2021: Frontiers in Pharmacology
Lujing Wang, Min Liu, Yucui Wu, Xingan Li, Fei Yin, Li Yin, Jianhui Liu
Obesity is a serious health issue as it is a social burden and the main risk factor for other metabolic diseases. Increasing evidence indicates that a high-fat diet (HFD) is the key factor for the development of obesity, but the key genes and their associated molecular mechanisms are still not fully understood. In this study, we performed integrated bioinformatic analysis and identified that fructose-1,6 biphosphatase 2 (FBP2) was involved in free fatty acids (FFAs)-induced lipid droplet accumulation in hepatocytes and HFD-induced obesity in mice...
May 11, 2021: Food & Function
Fang Wang, Yan Liao, Ming Zhang, Yue Zhu, Wenjin Wang, Hongshi Cai, Jianfeng Liang, Fan Song, Chen Hou, Shuojin Huang, Yadong Zhang, Cheng Wang, Jinsong Hou
N6-methyladenosine (m6 A) is the most abundant internal mRNA modification in eukaryotes and plays an important role in tumorigenesis. However, the underlying mechanism remains largely unclear. Here, we established a cell model of rapamycin-induced autophagy to screen m6 A-modifying enzymes. We found that m6 A demethylase fat mass and obesity-associated protein (FTO) plays a key role in regulating autophagy and tumorigenesis by targeting the gene encoding eukaryotic translation initiation factor gamma 1 (eIF4G1) in oral squamous cell carcinoma (OSCC)...
May 10, 2021: Oncogene
Wenneke van Weelden, Paul T Seed, Elie Antoun, Keith M Godfrey, Negusse T Kitaba, Karen A Lillycrop, Kathryn V Dalrymple, Agata Sobczyńska-Malefora, Rebecca C Painter, Lucilla Poston, Sara L White, Angela C Flynn
Recent studies implicate maternal gestational diabetes mellitus (GDM) in differential methylation of infant DNA. Folate and vitamin B12 play a role in DNA methylation, and these vitamins may also influence GDM risk. The aims of this study were to determine folate and vitamin B12 status in obese pregnant women and investigate associations between folate and vitamin B12 status, maternal dysglycaemia and neonatal DNA methylation at cytosine-phosphate-guanine sites previously observed to be associated with dysglycaemia...
May 11, 2021: Journal of Developmental Origins of Health and Disease
Adelheid Soubry, Susan K Murphy, Greet Vansant, Yang He, Thomas M Price, Cathrine Hoyo
Animal experiments have demonstrated that diets high in fats create a harmful environment for developing sperm cells, contributing to impaired reproductive health and induced risk for chronic diseases in the next generation. Changes at the level of the epigenome have been suggested to underlie these observations. Human data are limited to verify this hypothesis. While we earlier demonstrated a link between male obesity and DNA methylation changes at imprinted genes in mature sperm cells and newborns, it is currently unknown if -or how- a paternal eating pattern (related to obesity) is related to indices for epigenetic inheritance...
2021: Frontiers in Endocrinology
Noemí Cabré, Fedra Luciano-Mateo, Douglas J Chapski, Gerard Baiges-Gaya, Salvador Fernández-Arroyo, Anna Hernández-Aguilera, Helena Castañé, Elisabet Rodríguez-Tomàs, Marta París, Fàtima Sabench, Daniel Del Castillo, Josep M Del Bas, Mercedes Tomé, Clément Bodineau, Alejandro Sola-García, José López-Miranda, Alejandro Martín-Montalvo, Raúl V Durán, Thomas M Vondriska, Manuel Rosa-Garrido, Jordi Camps, Javier A Menéndez, Jorge Joven
BACKGROUND & AIMS: A holistic insight on the relationship between obesity and metabolic dysfunction-associated fatty liver disease is an unmet clinical need. Omics investigations can be used to investigate the multifaceted role of altered mitochondrial pathways to promote nonalcoholic steatohepatitis, a major risk factor for liver disease-associated death. There are no specific treatments but remission via surgery might offer an opportunity to examine the signaling processes that govern the complex spectrum of chronic liver diseases observed in extreme obesity...
May 4, 2021: Journal of Hepatology
Li Chen, Xiaojing Liu, Hao Zhou, Guoyong Li, Fangyang Huang, Jialiang Zhang, Tianli Xia, Wenhua Lei, Jiahao Zhao, Changming Li, Mao Chen
Lipid overload is intimately connected with the change of endothelial epigenetic status which impacts cellular signaling activities and endothelial function. Activating transcription factor 4 (ATF4) is involved in the regulation of lipid metabolism and meanwhile an epigenetic modifier. However, the role of ATF4 in the angiogenesis under lipid overload is not well understood. Here, to induce lipid overload status, we employed high-fat diet (HFD)-induced obese mouse model in vivo and palmitic acid (PA) to stimulate endothelial cells in vitro...
June 2021: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Ying Dong Du, Wen Yuan Guo, Cong Hui Han, Ying Wang, Xiao Song Chen, Da Wei Li, Jin Long Liu, Ming Zhang, Nan Zhu, Xin Wang
Despite N6-methyladenosine (m6A) is functionally important in various biological processes, its role and the underlying regulatory mechanism in the liver remain largely unexplored. In the present study, we showed that fat mass and obesity-associated protein (FTO, an m6A demethylase) was involved in mitochondrial function during hepatic ischemia-reperfusion injury (HIRI). We found that the expression of m6A demethylase FTO was decreased during HIRI. In contrast, the level of m6A methylated RNA was enhanced. Adeno-associated virus-mediated liver-specific overexpression of FTO (AAV8-TBG-FTO) ameliorated the HIRI, repressed the elevated level of m6A methylated RNA, and alleviated liver oxidative stress and mitochondrial fragmentation in vivo and in vitro...
May 4, 2021: Cell Death & Disease
Luis A Garcia, Samantha E Day, Richard L Coletta, Baltazar Campos, Tonya R Benjamin, Eleanna De Filippis, James A Madura, Lawrence J Mandarino, Lori R Roust, Dawn K Coletta
BACKGROUND: The mechanisms of weight loss and metabolic improvements following bariatric surgery in skeletal muscle are not well known; however, epigenetic modifications are likely to contribute. The aim of our study was to investigate skeletal muscle DNA methylation after weight loss induced by Roux-en-Y gastric bypass (RYGB) surgery. Muscle biopsies were obtained basally from seven insulin-resistant obese (BMI > 40 kg/m2 ) female subjects (45.1 ± 3.6 years) pre- and 3-month post-surgery with euglycemic hyperinsulinemic clamps to assess insulin sensitivity...
May 1, 2021: Clinical Epigenetics
Rafael S Lima, Rafael T Mattos, Nayara I Medeiros, Fabiana M Kattah, Julya R S Nascimento, Carlos A Menezes, Fabricio Rios-Santos, Walderez O Dutra, Juliana A S Gomes, Paula R Moreira
Childhood obesity is a global and increasing health issue. Inflammation and dysregulated adipose tissue secretion are common findings in obesity and have been related to poor metabolic function. Given that DNA methylation impacts gene expression and is responsive to environmental changes, we aimed, in addition to characterize the patients in anthropometric and biochemical terms, to determine the expression of cytokines and adipokines, assess the methylation on regulatory regions of the genes that code for these molecules, and investigate the association of the expression and gene methylation with anthropometric and biochemical parameters in childhood obesity...
April 26, 2021: Cytokine
Andrea Stoccoro, Fabio Coppedè
Epigenetic modifications of the nuclear genome, including DNA methylation, histone modifications and non-coding RNA post-transcriptional regulation, are increasingly being involved in the pathogenesis of several human diseases. Recent evidence suggests that also epigenetic modifications of the mitochondrial genome could contribute to the etiology of human diseases. In particular, altered methylation and hydroxymethylation levels of mitochondrial DNA (mtDNA) have been found in animal models and in human tissues from patients affected by cancer, obesity, diabetes and cardiovascular and neurodegenerative diseases...
April 27, 2021: International Journal of Molecular Sciences
Mariana Lizbeth Rodríguez-López, José Jaime Martínez-Magaña, David Ruiz-Ramos, Ana Rosa García, Laura Gonzalez, Carlos Alfonso Tovilla-Zarate, Emmanuel Sarmiento, Isela Esther Juárez-Rojop, Humberto Nicolini, Thelma Beatriz Gonzalez-Castro, Alma Delia Genis-Mendoza
Binge-eating disorder, recently accepted as a diagnostic category, is differentiated from bulimia nervosa in that the former shows the presence of binge-eating episodes and the absence of compensatory behavior. Epigenetics is a conjunct of mechanisms (like DNA methylation) that regulate gene expression, which are dependent on environmental changes. Analysis of DNA methylation in eating disorders shows that it is reduced. The present study aimed to analyze the genome-wide DNA methylation differences between individuals diagnosed with BED and BN...
April 22, 2021: Nutrients
Ayşegül Gemici, Osman Sinen, Mehmet Bülbül
Exposure to high fat diet during perinatal period (PHFD) leads to neuroplastic changes in autonomic circuits, however, the role of gender has been incompletely understood. This study aims to investigate (i) short, and (ii) long-term effects of PHFD on autonomic outflow, and (iii) sexual dimorphic variations emerge at adulthood. Male and female rats were fed a control diet (13.5 % kcal from fat) or PHFD (60 % kcal from fat) from embryonic day-14 to postnatal day-21. To assess changes in autonomic outflow, heart rate variability (HRV) was analyzed at 10- and 20-week-old ages...
April 29, 2021: Metabolic Brain Disease
Suhas Sureshchandra, Norma Mendoza, Allen Jankeel, Randall M Wilson, Nicole E Marshall, Ilhem Messaoudi
Pregravid obesity has been shown to disrupt the development of the offspring's immune system and increase susceptibility to infection. While the mechanisms underlying the impact of maternal obesity on fetal myeloid cells are emerging, the consequences for T cells remain poorly defined. In this study, we collected umbilical cord blood samples from infants born to lean mothers and mothers with obesity and profiled CD4 T cells using flow cytometry and single cell RNA sequencing at resting and following ex vivo polyclonal stimulation...
2021: Frontiers in Immunology
Zhi Xin Yau-Qiu, Francisco Madrid-Gambin, Lorraine Brennan, Andreu Palou, Ana María Rodríguez
SCOPE: Perinatal nutritional factors can program offspring metabolic phenotype and risk to obesity. We investigated the potential role of leptin supplementation (during lactation) in ameliorating the malprogrammed effects caused by mild maternal calorie restriction during gestation, on young rat offspring liver metabolic response. METHODS AND RESULTS: Untargeted and targeted metabolomics studies on liver samples were performed by NMR and GC-MS, respectively. Global DNA methylation and the expression by RT-PCR of key genes involved in different pathways were also determined...
April 26, 2021: Molecular Nutrition & Food Research
Kaiju Sun, Yangyang Du, Yuzhu Hou, Mingyue Zhao, Jiajia Li, Yazhe Du, Lingxiao Zhang, Changbao Chen, Hongmei Yang, Fei Yan, Rui Su
Purpose: The implementation of targeted therapies for acute myeloid leukemia (AML) has been challenging. Fat mass and obesity associated protein (FTO), an mRNA N6 -methyladenosine (m6 A) demethylase, functions as an oncogene that promotes leukemic oncogene-mediated cell transformation and leukemogenesis. Here, we investigated the role of Saikosaponin-d (SsD) in broad anti-proliferation effects in AML and evaluated the m6 A demethylation activity by targeting FTO of SsD. Methods: It was examined whether and how SsD regulates FTO/m6 A signaling in AML...
2021: Theranostics
Chengming Guo, Hongjin Chu, Zhaohua Gong, Bo Zhang, Chen Li, Jian Chen, Liuye Huang
AIMS: This study aimed at exploring HOXB13 expression and function in gastric cancer (GC), and the underlying molecular mechanism. MATERIALS AND METHODS: HOXB13 and fat mass and obesity-associated protein (FTO) expression in GC and non-GC tissues of GC patients were analyzed using Gene Expression Profiling Interactive Analysis (GEPIA) and verified by quantitative reverse transcription-polymerase chain reaction (RT-qPCR) and western blotting. The regulatory relationship between FTO and HOXB13 was verified via RT-qPCR, methylated RNA immunoprecipitation sequencing (MeRIP-seq), and double luciferase reporter gene assay...
April 21, 2021: Life Sciences
Bonnie Ho-Yee Yeung, Kelly Griffiths, Liron Berger, Omkar Paudel, Mi-Kyung Shin, Liangyou Rui, James S K Sham, Vsevolod Y Polotsky, Wan-Yee Tang
Obesity elevates plasma level of leptin, which has been associated with hypertension. Our recent studies in mice demonstrated that leptin increases blood pressure by activating the carotid sinus nerve, which transmits the chemosensory input from carotid bodies (CB) to the medullary centers; and the effect of leptin is mediated via transient receptor potential melastatin 7 (Trpm7) channels in CB glomus cells. We also found that Trpm7 overexpression and Trpm7 promoter demethylation in CB correlate positively with the hyperleptinemia and leptin receptor overexpression in CB...
April 23, 2021: American Journal of Respiratory Cell and Molecular Biology
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