scholarly journals Choline Supplementation in Obese Mouse Dams Alters Offspring DNA Methylation in a Time-Specific Manner

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 763-763
Author(s):  
Xinyin Jiang ◽  
Hunter Korsmo ◽  
Moshe Dembitzer ◽  
Sarah Khaldi ◽  
Shameera Sheeraz

Abstract Objectives Maternal obesity has long-term influence on metabolic health of offspring, partly through an epigenetic mechanism. Choline is a methyl donor which provides methyl groups for epigenetic modification such as DNA methylation. In this study, we examined the effect of maternal choline supplementation (MCS) on DNA methylation of offspring born to high-fat (HF) fed obese mouse dams. Methods C57BL/6J mice were fed either a 10% kcal normal fat (NF) or a 60% kcal HF diet with either 25 mM choline supplement or control drinking water from 4 weeks prior to mating until the end of gestation. The offspring were fed the HF diet for 6 weeks after weaning. We measured both global DNA methylation and site-specific methylation of several metabolic genes in the liver, visceral adipose tissue, and brain at both embryonic day E17.5 and after the post-weaning HF feeding. Results At E17.5, HF-MCS led to higher global DNA methylation in both fetal liver and brain. Methylation of one of the CpGs in the promoter region of Srebp1f (a gene that regulates lipogenesis) was also upregulated in the fetal liver by HF-MCS, accordingly there was lower expression of this gene (p < 0.05). However, HF-MCS had opposite effects on global DNA methylation after 6 weeks of post weaning HF feeding than during the fetal period. At this time point, HF-MCS led to hypomethylation of liver and visceral adipose tissue (p < 0.05). Global DNA methylation of the brain was decreased by post-weaning HF feeding but was not affected by maternal HF or MCS (p < 0.01). Conclusions In conclusion, MCS during maternal obesity in the perinatal period influences offspring DNA methylation in a time-specific manner. The epigenetic programming effect of MCS needs to be evaluated in both short and long term in the offspring. Funding Sources NIGMS.

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Sonsoles Morcillo ◽  
Ana B. Crujeiras ◽  
Lidia Sánchez-Alcoholado ◽  
Mercedes Clemente-Postigo ◽  
...  

Obesity Facts ◽  
2010 ◽  
Vol 3 (2) ◽  
pp. 7-7 ◽  
Author(s):  
Dirk Vissers ◽  
An Verrijken ◽  
Ilse Mertens ◽  
Caroline Van Gils ◽  
Annemie Van de Sompel ◽  
...  

2021 ◽  
Author(s):  
Luise Müller ◽  
Lena Gras ◽  
Anne Hoffmann ◽  
Tobias Hagemann ◽  
Stephan H. Bernhart ◽  
...  

Author(s):  
Helen Sievert ◽  
Christin Krause ◽  
Cathleen Geißler ◽  
Martina Grohs ◽  
Alexander T. El-Gammal ◽  
...  

Abstract Objective The risk to develop type 2 diabetes increases with the amount of visceral adiposity presumably due to increased lipolysis and subsequent lipid accumulation in visceral organs. However, data describing the molecular regulation of these pathways in humans are rare. We tested if genes of the lipogenic and lipolytic pathways are associated with glucose intolerance independently of obesity in visceral adipose tissue (VAT) of obese subjects. Moreover, we studied DNA methylation of FASN (fatty acid synthase), that catalyses the synthesis of long-chain fatty acids, in VAT of the same subjects and whether it is associated with metabolic traits. Subjects and methods Visceral adipose tissue biopsies and blood samples were taken from 93 severely obese subjects undergoing bariatric surgery. Subjects were grouped in low HbA1c (L-HbA1c, HbA1c<6.5 %) and high HbA1c (H-HbA1c, HbA1c≥6.5 %) groups and expression of genes from the lipogenic and lipolytic pathways was analysed by TaqMan qPCR. DNA methylation of FASN was quantified by bisulfite-pyrosequencing. Results FASN expression was downregulated in visceral fat from subjects with high HbA1c (p = 0.00009). Expression of other lipogenetic (SCD, ELOVL6) or lipolytic genes (ADRB3, PNPLA2) and FABP4 was not changed. DNA methylation of FASN was increased at a regulatory ChoRE recognition site in the H-HbA1c-subgroup and correlated negatively with FASN mRNA (r = − 0.302, p = 0.0034) and positively with HbA1c (r = 0.296, p = 0.0040) and blood glucose (r = 0.363, p = 0.0005). Conclusions Epigenetic downregulation of FASN in visceral adipose tissue of obese subjects might contribute to limited de novo lipogenesis of important insulin sensitizing fatty acids and could thereby contribute to glucose intolerance and the development of type 2 diabetes independently of obesity.


2019 ◽  
Vol 8 (1) ◽  
pp. 87 ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Isabel Moreno-Indias ◽  
Lidia Sanchez-Alcoholado ◽  
Bruno Ramos-Molina ◽  
Juan Alcaide-Torres ◽  
...  

Metabolic syndrome (MetS) has been postulated to increase the risk for type 2 diabetes, cardiovascular disease and cancer. Adipose tissue (AT) plays an important role in metabolic homeostasis, and AT dysfunction has an active role in metabolic diseases. MetS is closely related to lifestyle and environmental factors. Epigenetics has emerged as an interesting landscape to evaluate the possible interconnection between AT and metabolic disease, since it can be modulated by environmental factors and metabolic status. The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue. LPL and TNF DNA methylation values were significantly different in the control-case comparisons, with higher and lower methylation respectively in the MetS group. Negative correlations were found between global DNA methylation (measured by LINE-1 methylation levels) and the metabolic deterioration and glucose levels. There were associations among variables of MetS, BMI, and HOMA-IR with DNA methylation at several CpG positions for the studied genes. In particular, there was a strong positive association between serum triglyceride levels (TG) with PPARA and LPL methylation levels. TNF methylation was negatively associated with the metabolic worsening and could be an important factor in preventing MetS occurrence according to logistic regression analysis. Therefore, global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation are related to the etiology of MetS and might explain in part some of the features associated to metabolic disorders.


2019 ◽  
Vol 11 (1) ◽  
pp. 37-43 ◽  
Author(s):  
Sergio De los Santos ◽  
Luis Antonio Reyes-Castro ◽  
Ramón Mauricio Coral-Vázquez ◽  
Juan Pablo Méndez ◽  
Marcela Leal-García ◽  
...  

AbstractObjective:To determine whether (-)-epicatechin (Epi) could decrease visceral adipose tissue and improve the metabolic profile of male offspring rats, after maternal obesity was induced by a high-fat diet (HFD).Design:Maternal obesity in albino Wistar rats was induced with a HFD, whereas male offspring were fed with chow diet throughout the study. Eight male offspring per group, from different litters, were randomly assigned to the experimental or to the control groups. In the experimental group, Epi was administered at a dose of 1 mg/kg of body weight to the male offspring twice daily for two weeks, beginning at postnatal day (PND).Main measures:Weight of visceral adipose tissue, adipocyte size, and several metabolic parameters.Results:Epi administration in the male offspring induced a significant decrease in the amount of visceral fat (11.61 g less, P < 0.05) and in the size of adipose cells (28% smaller, P < 0.01). Besides, Epi was able to decrease insulin, leptin, and Homeostasis Model Assessment -Insulin Resistance (HOMA-IR) (P < 0.05), as well as triglycerides, when the experimental group was compared to the untreated male offspring of obese rats (P < 0.01).Conclusions:Epi administration can reverse the negative effects that maternal obesity has on the male offspring. This could be because Epi reduces the amount of visceral fat and improves metabolic profile.


2014 ◽  
Vol 2014 (1) ◽  
pp. 2680 ◽  
Author(s):  
Gloria Chi* ◽  
Yongmei Liu ◽  
James MacDonald ◽  
R. Graham Barr ◽  
Kathleen Donohue ◽  
...  

2018 ◽  
Vol 199 (4S) ◽  
Author(s):  
Karen Stern ◽  
Sherif Armanyous ◽  
Erick Remer ◽  
Ryan Ward ◽  
Joshua Augustine ◽  
...  

2019 ◽  
Author(s):  
Matthew D. Barberio ◽  
Evan P. Nadler ◽  
Samantha Sevilla ◽  
Rosemary Lu ◽  
Brennan Harmon ◽  
...  

AbstractBackgroundEpigenetic changes in visceral adipose tissue (VAT) with obesity and their effects on gene expression are poorly understood, especially during emergent obesity in youth. The current study tested the hypothesis that methylation and gene expression profiles of key growth factor and inflammatory pathways such as PI3K/AKT signaling are altered in VAT from obese compared to non-obese youth.MethodsVAT samples from adolescent females grouped as Lean (L; n=15; age=15±3 yrs, BMI=21.9±3.0 kg/m2) or Obese (Ob; n=15, age=16±2 yrs, BMI=45.8±9.8 kg/m2) were collected. Global methylation (n=20) and gene expression (N=30) patterns were profiled via microarray and interrogated for differences between groups by ANCOVA (p<0.05), followed by biological pathway analysis.ResultsOverlapping differences in methylation and gene expression in 317 genes were found in VAT from obese compared to lean groups. PI3K/AKT Signaling (p=1.83×10−6; 10/121 molecules in dataset/pathway) was significantly overrepresented in Ob VAT according to pathway analysis. mRNA upregulations in the PI3K/AKT Signaling Pathway genes TFAM (p=0.03; Fold change=1.8) and PPP2R5C (p=0.03, FC=2.6) were confirmed via qRT-PCR.ConclusionOur analyses show obesity-related differences in DNA methylation and gene expression in visceral adipose tissue of adolescent females. Specifically, we identified methylation site/gene expression pairs differentially regulated and mapped these differences to PI3K/AKT signaling, suggesting that PI3K/AKT signaling pathway dysfunction in obesity may be driven in part by obesity-related changes in DNA methylation.


Author(s):  
Hyunhwa Lee ◽  
Sungchul Lee ◽  
Ipuna Black ◽  
Laura Salado ◽  
Jonica Estrada ◽  
...  

People who suffer a mild traumatic brain injury (mTBI) have heterogeneous symptoms and disease trajectories, which make it difficult to precisely diagnose and assess complications long-term. Insufficient information is available regarding how to precisely diagnose and assess mTBI. This study identified and compared deficits in cognitive, psychosocial, visual functions, and balance performance between college students with and without histories of mTBI. Global DNA methylation ratio (5-mC%) in blood was also compared as a peripheral epigenetic marker. Twenty-five volunteers participated in this pilot study, including 11 mTBI cases (27.3% females; mean age of 28.7 years, SD=5.92) and 14 healthy controls (64.3% females; mean age of 22.0, SD=4.13). All the participants were assessed for cognitive (by NIH toolbox&mdash;executive function, memory, and processing speed), psychological (by PROMIS&mdash;depression, anxiety, and sleep disturbances), visual function (by King-Devick and binocular accommodative tests), postural balance performance (by a force plate), and blood 5-mC% (global methylation) levels. Students with mTBI reported significantly poorer episodic memory, severe anxiety, and more sleep disturbance problems. They also had higher blood 5-mC% level (all p&rsquo;s&lt;.05). No significant differences were found in visual function and postural balance. These findings validate changes in cognitive, psychosocial, and global DNA methylation long after mTBI.


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