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
Sandra Aparecida Benite-Ribeiro, Valkíria Alves de Lima Rodrigues, Mônica Rodrigues Ferreira Machado
The prevalence of obesity is increasing in nowadays societies and, despite being a multifactorial disease, it has a significant correlation with food intake. The control of food intake is performed by neurons of the arcuate nucleus of the hypothalamus (ARC), which secret orexigenic and anorexigenic neuropeptides, such as proopiomelanocortin (POMC), under stimulation of, e.g., ghrelin, insulin, and leptin. Insulin, uses inositol 1,4,5-trisphosphate/serine-threonine kinase (IP3/Akt) pathways and stimulates the exclusion of (Forkhead box protein O1) FOXO1 from the nucleus and thereby does the inactivation of the inhibition of POMC expression, while Leptin stimulates signal transducer and activator of transcription 3 (STAT3) phosphorylation and POMC expression...
April 20, 2021: Molecular Biology Reports
Keyong Deng, Xiaotong Ning, Xiaoxiao Ren, Bin Yang, Jianxin Li, Jie Cao, Jichun Chen, Xiangfeng Lu, Shufeng Chen, Laiyuan Wang
Aim: To reveal transcriptome-wide N6-methyladenosine (m6 A) methylome of coronary artery disease (CAD). Materials & methods: The m6 A levels of RNA from peripheral blood mononuclear cells measured by colorimetry were significantly decreased in CAD cases. Transcriptome-wide m6 A methylome profiled by methylated RNA immunoprecipitation sequencing (MeRIP-seq) identified differentially methylated m6 A sites within both mRNAs and lncRNAs between CAD and control group. Results: Bioinformatic analysis indicated that differentially methylated genes were involved in the pathogenesis of atherosclerosis...
April 20, 2021: Epigenomics
Jin Tae Kim, Hong Jin Lee, Hee-Seok Lee
Various chemicals containing pesticides can induce adipogenesis and cause obesity. Organophosphorus pesticides have been used for pest control. Here, we investigated the estrogen receptor (ER)-dependent adipogenesis-inducing effect of representative organophosphorus pesticides (OPs), diazinon, phoxim, terbufos and tolclofos-methyl in 3T3-L1 adipocytes. Four OPs exhibited ER agonistic effect, determined using the OECD Performance Based Test Guideline No. 455; in vitro ER stably transfected transactivation assay using ERα-HeLa-9903 cell line, through binding affinity to ERα...
April 10, 2021: Environmental Pollution
Ryu Miura, Atsuko Ikeda-Araki, Toru Ishihara, Kunio Miyake, Chihiro Miyashita, Tamie Nakajima, Sumitaka Kobayashi, Mayumi Ishizuka, Takeo Kubota, Reiko Kishi
Prenatal exposure to phthalates negatively affects the offspring's health. In particular, epigenetic alterations, such as DNA methylation, may connect phthalate exposure with health outcomes. Here, we evaluated the association of di-2-ethylhexyl phthalate (DEHP) exposure in utero with cord blood epigenome-wide DNA methylation in 203 mother-child pairs enrolled in the Hokkaido Study on Environment and Children's Health, using the Illumina HumanMethylation450 BeadChip. Epigenome-wide association analysis demonstrated the predominant positive associations between the levels of the primary metabolite of DEHP, mono(2-ethylhexyl) phthalate (MEHP), in maternal blood and DNA methylation levels in cord blood...
April 16, 2021: Science of the Total Environment
Omar Ramos-Lopez, Iñaki Milton-Laskibar, J Alfredo Martínez
PURPOSE OF REVIEW: The purpose of this article is to rationally review and critically appraise the current knowledge in the most relevant nongenetic and genetic factors influencing obesity predisposition. This information may be translated into the implementation of personalized nutrition approaches involving precision nutrigenetic and nutrigenomic strategies for obesity monitoring and weight management. RECENT FINDINGS: The importance and influence of several nongenetic contributors to obesity onset and individual responses to weight-loss interventions have been highlighted including the role of age, sex or perinatal feeding and others related to an individual's lifestyle and modifiable...
April 14, 2021: Current Opinion in Clinical Nutrition and Metabolic Care
Rosaria V Giglio, Anca P Stoian, Angelo M Patti, Ali A Rizvi, Vasily Sukhorukov, Marcello Ciaccio, Alexander Orekhov, Manfredi Rizzo
BACKGROUND: Metabolic syndrome is a clinical condition that deserves special attention because it puts the individual at high cardiovascular risk, especially heart attack and stroke. Considering the precision medicine, it would be advisable to valuate the individual cardio-metabolic risk by estimating the coesistence of risk factors (abdominal obesity, low level of High- Density Lipoprotein Cholesterol, High Triglycerides, and small dense Low-Density Lipoproteins sub-classes, hypertension, and elevated fasting glycemia), which could engrave on metabolism increasing cardiovascular mortality...
April 12, 2021: Current Pharmaceutical Design
Yoon Jeong Park, Sangseon Lee, Sangsoo Lim, Hahn Nahmgoong, Yul Ji, Jin Young Huh, Assim A Alfadda, Sun Kim, Jae Bum Kim
White adipose tissue (WAT) is a key regulator of systemic energy metabolism, and impaired WAT plasticity characterized by enlargement of preexisting adipocytes associates with WAT dysfunction, obesity, and metabolic complications. However, the mechanisms that retain proper adipose tissue plasticity required for metabolic fitness are unclear. Here, we comprehensively showed that adipocyte-specific DNA methylation, manifested in enhancers and CTCF sites, directs distal enhancer-mediated transcriptomic features required to conserve metabolic functions of white adipocytes...
March 16, 2021: Proceedings of the National Academy of Sciences of the United States of America
Amit Kumar, Ronald A Lubet, Jennifer T Fox, William G Nelson, Harold Seifried, Clinton J Grubbs, Mark Steven Miller
Epidemiology, clinical and experimental animal studies suggest high fructose diets are detrimental to metabolic status and may contribute to tumor development. This due to increased obesity and metabolic syndrome, known risk factors for many types of cancer. We compared tumor development in N-methyl-N-nitrosourea (MNU)-treated rats fed either a high (60%)-fructose diet (HFD) or a standard diet (SD). Female Sprague-Dawley rats at 43 days of age (DOA) were fed a SD or HFD followed by administration of MNU at 50 DOA...
2021: Journal of obesity and chronic diseases
Yaoyao Xia, Fang He, Xiaoyan Wu, Bie Tan, Siyuan Chen, Yuexia Liao, Ming Qi, Shuai Chen, Yuanyi Peng, Yulong Yin, Wenkai Ren
Accumulating evidence shows that nervous system governs host immune responses; however, how γ-aminobutyric acid (GABA)ergic system shapes the function of innate immune cells is poorly defined. Here, we demonstrate that GABA transporter (GAT2) modulates the macrophage function. GAT2 deficiency lowers the production of interleukin-1β (IL-1β) in proinflammatory macrophages. Mechanistically, GAT2 deficiency boosts the betaine/S-adenosylmethionine (SAM)/hypoxanthine metabolic pathway to inhibit transcription factor KID3 expression through the increased DNA methylation in its promoter region...
April 2021: Science Advances
Matheus Credendio Eiras, Daniel Pascoalino Pinheiro, Kalil Andrade Mubarac Romcy, Rui Alberto Ferriani, Rosana Maria Dos Reis, Cristiana Libardi Miranda Furtado
Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting approximately 5-20% of women of reproductive age. PCOS is a multifactorial, complex, and heterogeneous disease, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries, which may lead to impaired fertility. Besides the reproductive outcomes, multiple comorbidities, such as metabolic disturbances, insulin resistance, obesity, diabetes, and cardiovascular disease, are associated with PCOS. In addition to the clear genetic basis, epigenetic alterations may also play a central role in PCOS outcomes, as environmental and hormonal alterations directly affect clinical manifestations and PCOS development...
April 7, 2021: Reproductive Sciences
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