scholarly journals DNA methylation map in circulating leukocytes mirrors subcutaneous adipose tissue methylation pattern: a genome-wide analysis from non-obese and obese patients

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
A. B. Crujeiras ◽  
A. Diaz-Lagares ◽  
J. Sandoval ◽  
F. I. Milagro ◽  
S. Navas-Carretero ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Methylation Pattern ◽  
Obese Patients ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Subcutaneous Adipose

scholarly journals Archaic adaptive introgression in TBX15/WARS2

2015 ◽  
Author(s):  
Fernando Racimo ◽  
David Gokhman ◽  
Matteo Fumagalli ◽  
Amy Ko ◽  
Torben Hansen ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Fat Distribution ◽  
Geographic Region ◽  
Adaptive Introgression ◽  
Genome Wide ◽  
Divergent Haplotype ◽  
Subcutaneous Adipose ◽  
Genome Wide Scan

AbstractA recent study conducted the first genome-wide scan for selection in Inuit from Greenland using SNP chip data. Here, we report that selection in the region with the second most extreme signal of positive selection in Greenlandic Inuit favored a deeply divergent haplotype that is closely related to the sequence in the Denisovan genome, and was likely introgressed from an archaic population. The region contains two genes, WARS2 and TBX15, and has previously been associated with adipose tissue differentiation and body-fat distribution in humans. We show that the adaptively introgressed allele has been under selection in a much larger geographic region than just Greenland. Furthermore, it is associated with changes in expression of WARS2 and TBX15 in multiple tissues including the adrenal gland and subcutaneous adipose tissue, and with regional DNA methylation changes in TBX15.

scholarly journals PO-185 Lifestyle intervention modify DNA methylation of adipose tissue in overweight and obese men with insomnia symptoms

2018 ◽  
Vol 1 (4) ◽  
Author(s):  
Na Wu ◽  
Xiangyu Zhai ◽  
Xiao Tan ◽  
Petri Wiklund ◽  
Sulin Cheng
Keyword(s):  
Dna Methylation ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Dietary Intervention ◽  
Exercise Intervention ◽  
Whole Genome ◽  
Genome Wide ◽  
Diet And Exercise ◽  
Subcutaneous Adipose ◽  
Insomnia Symptoms

Objective To study whether diet and exercise intervention affect sleep and obesity-related genes’ DNA methylation in overweight and obese men with insomnia symptoms Methods The study participants were a subgroup of a large intervention and consisted of 10 overweight or obesity men aged 34-65 years with insomnia symptoms. They participated in a 6-month progressive aerobic exercise training and individualized dietary consoling program and were randomly selected from diet (n=4), exercise (n=3) and control (n=3) groups. Body composition included fat mass and lean mass in the whole body and abdominal android region were assessed by dual-energy X-ray densitometry. The fitness level (VO2max) was determined by 2-km walk test using a standard protocol. Blood samples from venous were taken at fasted state in the morning. Total cholesterol, high density lipid cholesterol, low density lipid cholesterol, triglycerides, glucose, insulin, non-esterified fatty acid, alanine aminotransferase, aspartate aminotransferase and γ-glutamyltransferase were assessed by conventional methods. Subcutaneous adipose tissue was taken from abdominal region before and after the intervention. DNA was extracted from subcutaneous adipose tissue using a QIAamp DNeasy Tissue Kit. Whole genome-wide DNA methylation was obtained using MethylRAD-Seq. MethylRAD library preparation started from DNA digestion by FspEI, then digested products were run on agarose gel to verify digestion and DNA ligase was added to the digestion solution. After ligation products amplication, PCR was conducted by MyCycler thermal cycler (Bio-Rad). The target fragment was excised from polyacrylamide gel and DNA was diffused from the gel in nuclease-free water. For relative quantification of MethylRAD data, DNA methylation levels were determined using the normalized read depth (reads per million, RPM) for each site. For each restriction site, its methylation level was estimated by dividing the log-transformed depth of each site by the log-transformed maximum depth (representing 100% methylation; i.e. M-index ¼ log(depth site)/ log(depth max)), where depth max was summarized from the top 2% of sites (approx. 500 for the standard library) with the highest sequencing coverage. Heat map images are generated with Matlab 7.0 software and pathways are analysed by WEB-based Gene SeT AnaLysis Toolket. A statistical significance for methylated CpGs and pathways were set to p=0.001 and p=0.05, respectively. Results No significant group differences by time were found in sleep-related variables, body composition, lifestyle factors nor with measured lipid and glucose biomarkers. However, whole genome-wide DNA methylation was decreased after dietary intervention, but was increased after exercise intervention, respectively. Correspondingly, 1253 and 708 differentially methylated loci were found in diet and exercise groups by contrast to the control group. Among them, the overlap genes between diet and exercise had multiple differentially methylated CpGs, including e.g. MYT1L (4 CpGs), CAMTA1 (3 CpGs), NRXN1 (3 CpGs), RPS6KA2 (3 CpGs), SEMA4D (3 CpGs). DNA methylation in PCDH8 was negatively correlated with wake after sleep onset after exercise intervention and MYRIP associated with sleep duration showed lower methylation after the dietary intervention. Further, 13 (DIO1, GCK, GYS1, LMNA, LY86, PNMT, PPARA, PPARD, SERPINE1, TH, TMEM18, TNFRSF1B and UBL5) and 2 (SDCCAG8 and TNF) obesity-related genes’ DNA methylation profile changed in response to diet and exercise, respectively. Percentage changes of CpGs within KLHDC8A, ANKS1A, FGFRL1 and KDM3B were correlated with energy yield fat and carbohydrate, HOMA-IR and VO2max, respectively. Conclusions We found that both exercise and dietary interventions have impacts on these genes related to sleep indicating by DNA methylation in PCDH8 and MYRIP, respectively. Further diet may be more effective than aerobic exercise intervention since greater number of modified obesity-related genes observed after dietary intervention. Our results indicate that reduce insomnia symptoms may need to more focus on control obesity.

Cefamandole Distribution in Serum, Adipose Tissue, and Wound Drainage in Morbidly Obese Patients

1986 ◽  
Vol 20 (11) ◽  
pp. 869-873 ◽  
Author(s):  
Henry J. Mann ◽  
Henry Buchwald
Keyword(s):  
Adipose Tissue ◽  
Rate Constant ◽  
Subcutaneous Adipose Tissue ◽  
Elimination Rate ◽  
Elimination Rate Constant ◽  
Morbidly Obese ◽  
Obese Patients ◽  
Tissue Concentrations ◽  
Wound Drainage ◽  
Subcutaneous Adipose

Distribution and elimination of cefamandole 2 g iv were studied in 11 morbidly obese patients during a gastric bypass operation and again on the first postoperative day. Serum, subcutaneous adipose tissue, wound drainage, and urine were analyzed by high performance liquid chromatography for cefamandole and pharmacokinetic parameters from the intraoperative period were compared to those obtained postoperatively. Total body clearance was significantly greater (p < 0.001) postoperatively (297 ml/min) than intraoperatively (254 ml/min). Volume changes were unpredictable but the elimination rate constant tended to increase postoperatively. Renal clearance and percentage of urinary recovery were significantly increased (p < 0.01) postoperatively. The patients had a mean (± SD) volume of the central compartment of 10.3 (± 2.3) L, volume at steady state of 18.3 (± 3.9) L, and elimination rate constant of 1.67 (± 0.63) h−1. Tissue concentrations of cefamandole were highest during the first hour after drug administration and were < 1 μg/g after 3.5 hours. Mean wound drainage concentrations ranged between 10 and 12 μg/ml during a dosing interval and dropped to 7 μg/ml 12 hours after the last dose. Intraoperative dosing of cefamandole is required to maintain subcutaneous adipose tissue concentrations > 1 μg/g during procedures longer than three hours in morbidly obese patients. A postoperative dose of cefamandole 2 g iv q6h will provide sustained and therapeutic concentrations in the wound drainage of morbidly obese patients.

scholarly journals A genome-wide analysis of DNA methylation identifies a novel association signal for Lp(a) concentrations in the LPA promoter

PLoS ONE ◽  
2020 ◽  
Vol 15 (4) ◽  
pp. e0232073
Author(s):  
Stefan Coassin ◽  
Natascha Hermann-Kleiter ◽  
Margot Haun ◽  
Simone Wahl ◽  
Rory Wilson ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Genome Wide Analysis ◽  
Genome Wide ◽  
A Genome ◽  
Novel Association

scholarly journals A Genome-Wide mQTL Analysis in Human Adipose Tissue Identifies Genetic Variants Associated with DNA Methylation, Gene Expression and Metabolic Traits

PLoS ONE ◽  
2016 ◽  
Vol 11 (6) ◽  
pp. e0157776 ◽  
Author(s):  
Petr Volkov ◽  
Anders H. Olsson ◽  
Linn Gillberg ◽  
Sine W. Jørgensen ◽  
Charlotte Brøns ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Genetic Variants ◽  
Human Adipose Tissue ◽  
Metabolic Traits ◽  
Genome Wide ◽  
A Genome

scholarly journals Multifaceted genome-wide study identifies novel regulatory loci for body mass index in Indians

2019 ◽  
Author(s):  
Anil K Giri ◽  
Gauri Prasad ◽  
Khushdeep Bandesh ◽  
Vaisak Parekatt ◽  
Anubha Mahajan ◽  
...  
Keyword(s):  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Subcutaneous Adipose Tissue ◽  
Regulatory Elements ◽  
Specific Gene ◽  
Genome Wide ◽  
Obesity Phenotype ◽  
Methylation Patterns ◽  
Subcutaneous Adipose

AbstractObesity, a risk factor for various human diseases originates through complex interactions between genes and prevailing environment that varies across populations. Indians exhibit a unique obesity phenotype likely attributed by specific gene pool and environmental factors. Here, we present genome-wide association study (GWAS) of 7,259 Indians to understand the genetic architecture of body mass index (BMI) in the population. Our study revealed novel association of variants in BAI3 (rs6913677) and SLC22A11 (rs2078267) at GWAS significance, and of ZNF45 (rs8100011) with near GWAS significance. As genetic loci may dictate the phenotype through modulation of epigenetic processes, we overlapped discovered genetic signatures with DNA methylation patterns of 236 Indian individuals, and analyzed expression of the candidate genes using publicly available data. The variants in BAI3 and SLC22A11 were found to dictate methylation patterns at unique CpGs harboring critical cis- regulatory elements. Further, BAI3, SLC22A11 and ZNF45 variants were found to overlie repressive chromatin, active enhancer, and active chromatin regions, in that order, in human subcutaneous adipose tissue in ENCODE database. Besides, the identified genomic regions represented potential binding sites for key transcription factors implicated in obesity and/or metabolic disorders. Interestingly, rs8100011 (ZNF45) acted as a robust cis-expression quantitative trait locus (cis-eQTL) in subcutaneous adipose tissue in GTEx portal, and ZNF45 gene expression showed an inverse correlation with BMI in skeletal muscle of Indian subjects. Further, gene-based GWAS analysis revealed CPS1 and UPP2 as additional leads regulating BMI in Indians. Our study decodes potential genomic mechanisms underlying obesity phenotype in Indians.

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