scholarly journals Integrative Analysis of Glucometabolic Traits, Adipose Tissue DNA Methylation, and Gene Expression Identifies Epigenetic Regulatory Mechanisms of Insulin Resistance and Obesity in African Americans

Diabetes ◽  
2020 ◽  
Vol 69 (12) ◽  
pp. 2779-2793
Author(s):  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
Timothy D. Howard ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
African Americans ◽  
Integrative Analysis ◽  
Regulatory Mechanisms

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

scholarly journals Integrative analysis of glucometabolic traits, adipose tissue DNA methylation and gene expression identifies epigenetic regulatory mechanisms of insulin resistance and obesity in African Americans

2020 ◽  
Author(s):  
Ada Admin ◽  
Neeraj K. Sharma ◽  
Mary E. Comeau ◽  
Dennis Montoya ◽  
Matteo Pellegrini ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
African Americans ◽  
Association Studies ◽  
Regulation Of Gene Expression ◽  
Transcript Level ◽  
Matsuda Index

Decline in insulin sensitivity due to dysfunction of adipose tissue (AT) is one of the earliest pathogenic events in Type 2 Diabetes. We hypothesize that differential DNA methylation (DNAm) controls insulin sensitivity and obesity by modulating transcript expression in AT. Integrating AT DNAm profiles with transcript profile data measured in a cohort of 230 African Americans from AAGMEx cohort, we performed <i>cis</i>-expression quantitative trait methylation (<i>cis</i>-eQTM) analysis to identify epigenetic regulatory loci for glucometabolic trait-associated transcripts. We identified significantly associated CpG-regions for 82 transcripts (FDR-P<0.05). The strongest eQTM locus was observed for the proopiomelanocortin (<i>POMC</i>; r= -0.632, P= 4.70X10<sup>-27</sup>) gene. Epigenome-wide association studies (EWAS) further identified 155, 46, and 168 CpG regions associated (FDR-P <0.05) with Matsuda index, S<sub>I</sub> and BMI, respectively. Intersection of EWAS, transcript level to trait association, and eQTM results, followed by causal inference test identified significant eQTM loci for 23 genes that were also associated with Matsuda index, S<sub>I </sub>and/or BMI in EWAS. These associated genes include <i>FERMT3</i>, <i>ITGAM</i>, <i>ITGAX</i>, and <i>POMC</i>. In summary, applying an integrative multi-omics approach, our study provides evidence for DNAm-mediated regulation of gene expression at both previously identified and novel loci for many key AT transcripts influencing insulin resistance and obesity.

scholarly journals Adipose tissue 11βHSD1 gene expression, βcell function and ectopic fat in obese African Americans versus Hispanics

Obesity ◽  
2013 ◽  
Vol 22 (1) ◽  
pp. 14-18 ◽  
Author(s):  
Lauren E. Gyllenhammer ◽  
Tanya L. Alderete ◽  
Swapna Mahurka ◽  
Hooman Allayee ◽  
Michael I. Goran
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
African Americans ◽  
Ectopic Fat

scholarly journals DNA methylation and gene expression of HIF3A: cross-tissue validation and associations with BMI and insulin resistance

2016 ◽  
Vol 8 (1) ◽  
Author(s):  
Ailsa Maria Main ◽  
Linn Gillberg ◽  
Anna Louisa Jacobsen ◽  
Emma Nilsson ◽  
Anette Prior Gjesing ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Dna Methylation

Abstract 6260: Up-Regulated Expression of MicroRNA-143 in Association with Obesity in the Adipose Tissue of Mice Fed High Fat Diet

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Rieko Takanabe ◽  
Koh Ono ◽  
Tomohide Takaya ◽  
Takahiro Horie ◽  
Hiromichi Wada ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Control Cell ◽  
High Fat ◽  
Expression Levels ◽  
Mesenteric Fat ◽  
Regulated Expression

Obesity is the result of an expansion and increase in the number of individual adipocytes. Since changes in gene expression during adipocyte differentiation and hypertrophy are closely associated with insulin resistance and cardiovascular diseases, further insight into the molecular basis of obesity is needed to better understand obesity-associated diseases. MicroRNAs (miRNAs) are approximately 17–24nt single stranded RNA, that post-transcriptionally regulate gene expression. MiRNAs control cell growth, differentiation and metabolism, and may be also involved in pathogenesis and pathophysiology of diseases. It has been proposed that miR-143 plays a role in the differentiation of preadipocytes into mature adipocytes in culture. However, regulated expression of miR-143 in the adult adipose tissue during the development of obesity in vivo is unknown. To solve this problem, C57BL/6 mice were fed with either high-fat diet (HFD) or normal chow (NC). Eight weeks later, severe insulin resistance was observed in mice on HFD. Body weight increased by 35% and the mesenteric fat weight increased by 3.3-fold in HFD mice compared with NC mice. We measured expression levels of miR-143 in the mesenteric fat tissue by real-time PCR and normalized with those of 5S ribosomal RNA. Expression of miR-143 in the mesenteric fat was significantly up-regulated (3.3-fold, p<0.05) in HFD mice compared to NC mice. MiR-143 expression levels were positively correlated with body weight (R=0.577, p=0.0011) and the mesenteric fat weight (R=0.608, p=0.0005). We also measured expression levels in the mesenteric fat of PPARγ and AP2, whose expression are deeply involved in the development of obesity, insulin resistant and arteriosclerosis. The expression levels of miR-143 were closely correlated with those of PPARγ (R=0.600, p=0.0040) and AP2 (R=0.630, p=0.0022). These findings provide the first evidence for up-regulated expression of miR-143 in the mesenteric fat of HFD-induced obese mice, which might contribute to regulated expression of genes involved in the pathophysiology of obesity.

scholarly journals Complement Factor C3 Methylation and mRNA Expression Is Associated to BMI and Insulin Resistance in Obesity

Genes ◽  
2018 ◽  
Vol 9 (8) ◽  
pp. 410 ◽  
Author(s):  
Daniel Castellano-Castillo ◽  
Isabel Moreno-Indias ◽  
Jose Carlos Fernandez-Garcia ◽  
Mercedes Clemente-Postigo ◽  
Manuel Castro-Cabezas ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Dna Methylation ◽  
Adipose Tissue ◽  
Messenger Rna ◽  
Density Lipoprotein ◽  
Complement Factor ◽  
Mrna Levels ◽  
Model Assessment ◽  
Tissue Samples ◽  
Obese Class

Epigenetic marks, and especially DNA methylation, are becoming an important factor in obesity, which could help to explain its etiology and associated comorbidities. Adipose tissue, now considered as an important endocrine organ, produces complement system factors. Complement component 3 (C3) turns out to be an important protein in metabolic disorders, via either inflammation or the C3 subproduct acylation stimulating protein (ASP) which directly stimulates lipid storage. In this study, we analyze C3 DNA methylation in adipose tissue from subjects with a different grade of obesity. Adipose tissue samples were collected from subjects with a different degree of obesity determined by their body mass index (BMI) as: Overweight subjects (BMI ≥ 25 and <30), obese class 1/2 subjects (BMI ≥ 30 and <40) and obese class 3 subjects (BMI ≥ 40). C3 DNA methylation was measured for 7 CpGs by pyrosequencition using the Pyromark technology (Qiagen, Madrid Spain). C3 messenger RNA (mRNA) levels were analyzed by pre-designed Taqman assays (Applied biosystems, Foster City, CA, USA) and ASP/C3a was measured using a ELISA kit. The data were analyzed using the statistic package SPSS. C3 DNA methylation levels were lower in the morbid obese group. Accordingly, C3 methylation correlated negatively with BMI and leptin. However, C3 mRNA levels were more associated with insulin resistance, and positive correlations with insulin, glucose and homeostasis model assessment-estimated insulin resistance (HOMA-IR) existed. ASP correlated negatively with high density lipoprotein (HDL) cholesterol. C3 methylation levels were associated to adiposity variables, such as BMI and leptin, while the C3 mRNA levels were associated to glucose metabolism.

scholarly journals Eicosapentaenoic acid actions on adiposity and insulin resistance in control and high-fat-fed rats: role of apoptosis, adiponectin and tumour necrosis factor-α

2007 ◽  
Vol 97 (2) ◽  
pp. 389-398 ◽  
Author(s):  
Patricia Pérez-Matute ◽  
Nerea Pérez-Echarri ◽  
J. Alfredo Martínez ◽  
Amelia Marti ◽  
María J. Moreno-Aliaga
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Body Weight Gain ◽  
Control Diet ◽  
Cafeteria Diet ◽  
High Fat ◽  
Beneficial Effects

n-3 PUFA have shown potential anti-obesity and insulin-sensitising properties. However, the mechanisms involved are not clearly established. The aim of the present study was to assess the effects of EPA administration, one of the n-3 PUFA, on body-weight gain and adiposity in rats fed on a standard or a high-fat (cafeteria) diet. The actions on white adipose tissue lipolysis, apoptosis and on several genes related to obesity and insulin resistance were also studied. Control and cafeteria-induced overweight male Wistar rats were assigned into two subgroups, one of them daily received EPA ethyl ester (1 g/kg) for 5 weeks by oral administration. The high-fat diet induced a very significant increase in both body weight and fat mass. Rats fed with the cafeteria diet and orally treated with EPA showed a marginally lower body-weight gain (P = 0·09), a decrease in food intake (P < 0·01) and an increase in leptin production (P < 0·05). EPA administration reduced retroperitoneal adipose tissue weight (P < 0·05) which could be secondary to the inhibition of the adipogenic transcription factor PPARγ gene expression (P < 0·001), and also to the increase in apoptosis (P < 0·05) found in rats fed with a control diet. TNFα gene expression was significantly increased (P < 0·05) by the cafeteria diet, while EPA treatment was able to prevent (P < 0·01) the rise in this inflammatory cytokine. Adiposity-corrected adiponectin plasma levels were increased by EPA. These actions on both TNFα and adiponectin could explain the beneficial effects of EPA on insulin resistance induced by the cafeteria diet.

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