Distinct Associations of BMI and Fatty Acids With DNA Methylation in Fasting and Postprandial States in Men

We have previously shown that blood global DNA methylation (DNAm) differs between postprandial state (PS) and fasting state (FS) and is associated with BMI and polyunsaturated fatty acid (PUFA) (negatively and positively, respectively) in 12 metabolically healthy adult Mexican men (AMM cohort) equally distributed among conventional BMI classes. Here, we detailed those associations at CpG dinucleotide level by exploiting the Infinium methylation EPIC array (Illumina). We sought differentially methylated CpG (dmCpG) that were (1) associated with BMI (BMI-dmCpG) and/or fatty acids (FA) (FA-dmCpG) in FS or PS and (2) different across FS and PS within a BMI class. BMI-dmCpG and FA-dmCpG were more numerous in FS compared to PS and largely prandial state-specific. For saturated and monounsaturated FA, dmCpG overlap was higher across than within the respective saturation group. Several BMI- and FA-dmCpG mapped to genes involved in metabolic disease and in some cases matched published experimental data sets. Notably, SETDB1 and MTHFS promoter dmCpG could explain the previously observed associations between global DNAm, PUFA content, and BMI in FS. Surprisingly, overlap between BMI-dmCpG and FA-dmCpG was limited and the respective dmCpG were differentially distributed across functional genomic elements. BMI-dmCpG showed the highest overlap with dmCpG of the saturated FA palmitate, monounsaturated C20:1 and PUFA C20:2. Of these, selected promoter BMI-dmCpG showed opposite associations with palmitate compared to C20:1 and C20:2. As for the comparison between FS and PS within BMI classes, dmCpG were strikingly more abundant and variably methylated in overweight relative to normoweight or obese subjects (∼70–139-fold, respectively). Overweight-associated dmCpG-hosting genes were significantly enriched in targets for E47, SREBP1, and RREB1 transcription factors, which are known players in obesity and lipid homeostasis, but none overlapped with BMI-dmCpG. We show for the first time that the association of BMI and FA with methylation of disease-related genes is distinct in FS and PS and that limited overlap exists between BMI- and FA-dmCpG within and across prandial states. Our study also identifies a transcriptional regulation circuitry in overweight that might contribute to adaptation to that condition or to transition to obesity. Further work is necessary to define the pathophysiological implications of these findings.

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Epigenetic Downregulation of FASN in Visceral Adipose Tissue of Insulin Resistant Subjects

Experimental and Clinical Endocrinology & Diabetes ◽

10.1055/a-1150-7446 ◽

2020 ◽

Author(s):

Helen Sievert ◽

Christin Krause ◽

Cathleen Geißler ◽

Martina Grohs ◽

Alexander T. El-Gammal ◽

...

Keyword(s):

Type 2 Diabetes ◽

Dna Methylation ◽

Fatty Acids ◽

Adipose Tissue ◽

Glucose Intolerance ◽

Visceral Adipose Tissue ◽

High Hba1c ◽

Obese Subjects ◽

Visceral Adipose

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.

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Characterising sex differences of autosomal DNA methylation in whole blood using the Illumina EPIC array

10.1101/2021.09.02.458717 ◽

2021 ◽

Author(s):

Olivia A Grant ◽

Yucheng Wang ◽

Meena Kumari ◽

Nicolae Radu Zabet ◽

Leonard C Schalkwyk

Keyword(s):

Dna Methylation ◽

Sex Differences ◽

Whole Blood ◽

Cpg Islands ◽

Disease Etiology ◽

Cpg Sites ◽

Males And Females ◽

Methylation Patterns ◽

First Time ◽

Epic Array

Sex differences are known to play a role in disease etiology, progression and outcome. Previous studies have revealed autosomal epigenetic differences between males and females in some tissues, including differences in DNA methylation patterns. Here, we report for the first time an analysis of autosomal sex differences in DNAme using the Illumina EPIC array in human whole blood (n=1171). We identified 554 sex-associated differentially methylated CpG sites (saDMPs) with the majority found to be hypermethylated in females (70%). These saDMP's are enriched in CpG islands and CpG shores and located preferentially at 5'UTRs, 3'UTRs and enhancers. Additionally, we identified 311 significant sex associated differentially methylated regions (saDMRs). Transcription factor binding site enrichment revealed enrichment of transcription factors related to critical developmental processes and sex determination such as SRY and SOX9. Our study reports a reliable catalogue of sex associated CpG sites and elucidates several characteristics of these sites.

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PHOSPHO1 Gene DNA Methylations are Associated with a Change in HDL-C Response to Simvastatin Treatment

Current Pharmaceutical Design ◽

10.2174/1381612826666200720234604 ◽

2020 ◽

Vol 26 (38) ◽

pp. 4944-4952 ◽

Cited By ~ 1

Author(s):

Juanlin Fan ◽

Qianru Cai ◽

Di Zhang ◽

Justin Weinstock ◽

Xiaoxiao Qu ◽

...

Keyword(s):

Dna Methylation ◽

Density Lipoprotein ◽

Significant Negative Correlation ◽

High Response ◽

Lipid Lowering ◽

Additive Interaction ◽

Simvastatin Treatment ◽

Obese Subjects ◽

Dna Methylations ◽

Response Group

Objective: Our aim was to detect the effects of DNA methylations in the phosphoethanolamine/ phosphocholine phosphatase (PHOSPHO1) gene on the therapeutic efficacy of simvastatin. Methods: We used an extreme sampling approach by selecting 211 individuals from approximately the top and bottom 15% of adjusted lipid-lowering response residuals to simvastatin (n=104 for the high response group and n=107 for the low response group) from a total of 734 subjects with hyperlipidemia. They received a daily oral dose of 20 mg simvastatin for eight consecutive weeks. DNA methylation loci at the PHOSPHO1 gene were measured using high-throughput next-generation sequencing-based sequencing technology. Fasting serum lipids were measured at baseline and after eight weeks of simvastatin treatment. Results: Mean PHOSPHO1 DNA methylation had a significant negative correlation with high-density lipoprotein cholesterol (HDL-C) variation (β=-0.014, P=0.045) in the high response group. After stratifying by body mass index (BMI), the associations between the PHOSPHO1 DNA methylations and the change in HDL-C in response to simvastatin were more significant in obese subjects with a BMI of 25 kg/m2 or higher (β=-0.027, P=0.002). Mean PHOSPHO1 methylation and traditional predictors could explain up to 24.7% (adjusted R2) of the change in HDL-C response in obese patients. There was a statistically significant additive interaction term (P=0.028) between BMI and mean PHOSPHO1 methylation in the model of the change in HDL-C in response to simvastatin. Conclusion: Our findings suggest that PHOSPHO1 DNA methylations are associated with a change in HDL-C in response to simvastatin treatment, and this association is especially dependent on the extent of patient obesity.

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DLR HySU—A Benchmark Dataset for Spectral Unmixing

Remote Sensing ◽

10.3390/rs13132559 ◽

2021 ◽

Vol 13 (13) ◽

pp. 2559

Author(s):

Daniele Cerra ◽

Miguel Pato ◽

Kevin Alonso ◽

Claas Köhler ◽

Mathias Schneider ◽

...

Keyword(s):

Spectral Unmixing ◽

Benchmark Dataset ◽

Data Sets ◽

Endmember Extraction ◽

Imaging Spectrometer ◽

Hyperspectral Unmixing ◽

Processing Step ◽

German Aerospace ◽

Spectrometer Data ◽

First Time

Spectral unmixing represents both an application per se and a pre-processing step for several applications involving data acquired by imaging spectrometers. However, there is still a lack of publicly available reference data sets suitable for the validation and comparison of different spectral unmixing methods. In this paper, we introduce the DLR HyperSpectral Unmixing (DLR HySU) benchmark dataset, acquired over German Aerospace Center (DLR) premises in Oberpfaffenhofen. The dataset includes airborne hyperspectral and RGB imagery of targets of different materials and sizes, complemented by simultaneous ground-based reflectance measurements. The DLR HySU benchmark allows a separate assessment of all spectral unmixing main steps: dimensionality estimation, endmember extraction (with and without pure pixel assumption), and abundance estimation. Results obtained with traditional algorithms for each of these steps are reported. To the best of our knowledge, this is the first time that real imaging spectrometer data with accurately measured targets are made available for hyperspectral unmixing experiments. The DLR HySU benchmark dataset is openly available online and the community is welcome to use it for spectral unmixing and other applications.

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Bioactive Compounds in Salicornia patula Duval-Jouve: A Mediterranean Edible Euhalophyte

Foods ◽

10.3390/foods10020410 ◽

2021 ◽

Vol 10 (2) ◽

pp. 410

Author(s):

Irene Sánchez-Gavilán ◽

Esteban Ramírez ◽

Vicenta de la Fuente

Keyword(s):

Fatty Acids ◽

Bioactive Compounds ◽

Mediterranean Area ◽

Biological Properties ◽

Total Phenolic ◽

Tinto River ◽

New Findings ◽

High Concentrations ◽

Salicornia Patula ◽

First Time

Many halophytes have great nutritional and functional potential, providing chemical compounds with biological properties. Salicornia patula Duval-Jouve is a common euhalophyte from saline Mediterranean territories (Spain, Portugal, France, and Italy). In the present work we quantified for the first time the bioactive compounds in S. patula (total phenolic compounds and fatty acids), from Iberian Peninsula localities: littoral-coastal Tinto River basin areas (southwest Spain, the Huelva province), and mainland continental territories (northwest and central Spain, the Valladolid and Madrid provinces). Five phenolic acids including caffeic, coumaric, veratric, salicylic, and transcinnamic have been found with differences between mainland and coastal saltmarshes. S. patula contain four flavonoids: quercetin-3-O-rutinoside, kaempferol/luteolin, apigenin 7-glucoside, and pelargonidin-3-O-rutinoside. These last two glycosylated compounds are described for the first time in this genus of Chenopodiaceae. The fatty acid profile described in S. patula stems contains palmitic, oleic, and linoleic acids in high concentrations, while stearic and long-chain fatty acids were detected in low amounts. These new findings confirm that S. patula is a valuable source of bioactive compounds from Mediterranean area.

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Insight into the Secondary Metabolites of Geum urbanum L. and Geum rivale L. Seeds (Rosaceae)

Plants ◽

10.3390/plants10061219 ◽

2021 ◽

Vol 10 (6) ◽

pp. 1219

Author(s):

Marek Bunse ◽

Peter Lorenz ◽

Florian C. Stintzing ◽

Dietmar R. Kammerer

Keyword(s):

Fatty Acids ◽

Phenolic Compounds ◽

Unsaturated Fatty Acids ◽

Asiatic Acid ◽

Cosmetic Products ◽

Nutritional Properties ◽

First Time ◽

Derivatives Of ◽

Geum Urbanum ◽

Insight Into

The present study aimed at the identification and quantitation of phenolic compounds, fatty acids, and further characteristic substances in the seeds of Geum urbanum L. and Geum rivale L. For this purpose, individual components of extracts recovered with MeOH, CH2Cl2, and by cold-pressing, respectively, were characterized by HPLC-DAD/ESI-MSn and GC/MS and compared with reference compounds. For both Geum species, phenolic compounds, such as flavonoids and gallic acid derivatives, and triterpenes, such as saponins and their aglycones, were detected. Surprisingly, both Geum species revealed the presence of derivatives of the triterpenoid aglycons asiatic acid and madecassic acid, which were characterized for the first time in the genus Geum. Furthermore, the fatty acids of both species were characterized by GC–MS after derivatization. Both species showed a promising fatty-acid profile in terms of nutritional properties because of high proportions of unsaturated fatty acids. Linoleic acid and linolenic acid were most abundant, among other compounds such as palmitic acid and stearic acid. In summary, the present study demonstrates the seeds of G. urbanum and G. rivale to be a valuable source of unsaturated fatty acids and bioactive phenolics, which might be exploited for nutritional and cosmetic products and for phytotherapeutic purposes.

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Natural Course of Metabolically Healthy Overweight/Obese Subjects and the Impact of Weight Change

Nutrients ◽

10.3390/nu8070430 ◽

2016 ◽

Vol 8 (7) ◽

pp. 430 ◽

Cited By ~ 8

Author(s):

Ruizhi Zheng ◽

Chengguo Liu ◽

Chunmei Wang ◽

Biao Zhou ◽

Yi Liu ◽

...

Keyword(s):

Weight Change ◽

Natural Course ◽

Obese Subjects ◽

Metabolically Healthy ◽

The Impact

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Abstract 17843: Visceral Adipose Tissue Secretion of Adiponectin Decreases with Increased Body Mass Index

Circulation ◽

10.1161/circ.130.suppl_2.17843 ◽

2014 ◽

Vol 130 (suppl_2) ◽

Author(s):

Lenore R Rengel ◽

Brittaney Obi ◽

Jon Gould ◽

Matthew Goldblatt ◽

Andrew Kastenmeier ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Metabolic Health ◽

Metabolically Healthy Obese ◽

Obese Subjects ◽

Healthy Obese ◽

Metabolically Healthy ◽

Visceral Adipose ◽

Subcutaneous Adipose

Introduction: Peripheral adiposity is associated with better metabolic health and higher plasma adiponectin (ADPN) levels. Since ADPN is secreted mainly by adipose tissue (AT), it is intriguing that higher visceral adipose tissue (VAT) is associated with lower ADPN levels and poor metabolic health. Hypothesis: We hypothesized that various AT depots differ in their ability to secrete ADPN. Methods: Paired AT samples (VAT and subcutaneous adipose tissue (SAT)) were collected from 19 subjects (10 women, 15 obese) undergoing elective abdominal surgery. The samples were cultured and the supernatant was collected after 24 hours. ADPN levels released into the supernatant from VAT and SAT were measured using multiplex methods. Subjects were defined as obese or non-obese (NO) based on BMI > or ≤ 30kg/m2 respectively. Obese subjects were further classified as metabolically unhealthy obese (MUO) or metabolically healthy obese (MHO) based on presence or absence of type 2 diabetes mellitus, hypertension, or cardiovascular disease at the time of surgery. Results: Mean ADPN secretion levels from SAT and VAT were similar in NO subjects (17.3 ± 3.4 vs. 9.8 ± 13.0 ng/mL/mg, p=0.5) whereas the mean ADPN secretion was lower from VAT among obese subjects (15.9 ± 0.8 vs. 4.5 ± 0.2 ng/mL/mg, p=0.0002). ADPN secretion decreased from VAT (r=-0.16) and increased from SAT (r=0.33) with increased BMI (Fig.1). When MHO and MUO were compared, ADPN secretion from VAT in MHO was reduced only slightly (16.1 ± 8.2 vs. 4.0 ± 2.0 ng/mL/mg, p=0.07) whereas ADPN secretion was significantly reduced in MUO (15.9 ± 5.3 vs. 4.7 ± 4.6 ng/mL/mg, p=0.003). Conclusions: Reduced ADPN secretion from VAT in subjects with increasing BMI may explain lower circulating ADPN levels in obese individuals. Higher ADPN production from SAT and the relatively preserved secretion of ADPN from VAT may explain metabolic health in some obese individuals. Futures studies will help identify factors that control ADPN secretion from AT.

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Diagnosis of COVID-19 using 3D CT scans and vaccination for COVID-19

World Journal of Engineering ◽

10.1108/wje-03-2021-0161 ◽

2021 ◽

Vol ahead-of-print (ahead-of-print) ◽

Author(s):

Gangadhar Ch ◽

S. Jana ◽

Sankararao Majji ◽

Prathyusha Kuncha ◽

Fantin Irudaya Raj E. ◽

...

Keyword(s):

Virus Isolate ◽

Research Work ◽

Three Dimensional ◽

Ct Scans ◽

Data Sets ◽

Content Type ◽

Infected People ◽

3D Data ◽

Ct Classification ◽

First Time

Purpose For the first time in a decade, a new form of pneumonia virus, coronavirus, COVID-19, appeared in Wuhan, China. To date, it has affected millions of people, killed thousands and resulted in thousands of deaths around the world. To stop the spread of this virus, isolate the infected people. Computed tomography (CT) imaging is very accurate in revealing the details of the lungs and allows oncologists to detect COVID. However, the analysis of CT scans, which can include hundreds of images, may cause delays in hospitals. The use of artificial intelligence (AI) in radiology could help to COVID-19-positive cancer in this manner is the main purpose of the work. Design/methodology/approach CT scans are a medical imaging procedure that gives a three-dimensional (3D) representation of the lungs for clinical purposes. The volumetric 3D data sets can be regarded as axial, coronal and transverse data sets. By using AI, we can diagnose the virus presence. Findings The paper discusses the use of an AI for COVID-19, and CT classification issue and vaccination details of COVID-19 have been detailed in this paper. Originality/value Originality of the work is, all the data can be collected genuinely and did research work doneown methodology.

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The Roles of Human DNA Methyltransferases and Their Isoforms in Shaping the Epigenome

Genes ◽

10.3390/genes10020172 ◽

2019 ◽

Vol 10 (2) ◽

pp. 172 ◽

Cited By ~ 35

Author(s):

Hemant Gujar ◽

Daniel Weisenberger ◽

Gangning Liang

Keyword(s):

Dna Methylation ◽

Cytosine Methylation ◽

De Novo ◽

Ring Finger ◽

Dna Methyltransferases ◽

Epigenetic Modifications ◽

Hard Copy ◽

Physiological Processes ◽

New Gene ◽

Cpg Dinucleotide

A DNA sequence is the hard copy of the human genome and it is a driving force in determining the physiological processes in an organism. Concurrently, the chemical modification of the genome and its related histone proteins is dynamically involved in regulating physiological processes and diseases, which overall constitutes the epigenome network. Among the various forms of epigenetic modifications, DNA methylation at the C-5 position of cytosine in the cytosine–guanine (CpG) dinucleotide is one of the most well studied epigenetic modifications. DNA methyltransferases (DNMTs) are a family of enzymes involved in generating and maintaining CpG methylation across the genome. In mammalian systems, DNA methylation is performed by DNMT1 and DNMT3s (DNMT3A and 3B). DNMT1 is predominantly involved in the maintenance of DNA methylation during cell division, while DNMT3s are involved in establishing de novo cytosine methylation and maintenance in both embryonic and somatic cells. In general, all DNMTs require accessory proteins, such as ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domain 1 (UHRF1) or DNMT3-like (DNMT3L), for their biological function. This review mainly focuses on the role of DNMT3B and its isoforms in de novo methylation and maintenance of DNA methylation, especially with respect to their role as an accessory protein.

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