Characteristics of Normal/Overweight and Obese groups.

<p>Values are given as average ± SEM for each group (34–36 per group) where N/Ow represents the normal/overweight group, with three obese groups (I, II and III of increasing obesity). Data were analyzed by ANOVA (or Chi² for metabolic syndrome distribution), followed by post-hoc test for comparison vs normal/overweight group where *p<0.05, **p<0.01 and ***p<0.0001 and p NS indicates not significant. ApoB and ApoA1, apolipoprotein B and A1; BMI, body mass index; Chol, cholesterol; DBP, diastolic blood pressure; SBP, systolic blood pressure; WC, waist circumference.</p>#<p>Parameters used for diagnosis of metabolic syndrome.</p

Plasma levels of C3a/C3adesArg and adiponectin and their relationship with subcutaneous C3 and C3aR mRNA gene expression levels.

<p>A) Plasma C3a/C3adesArg and B) adiponectin in Normal/overweight (N/Ow) group and increasing obesity groups. Plasma C3a/C3adesArg correlates negatively with C3 (C) and C3aR (E) gene expression whereas adiponectin correlates positively with C3 (D) and C3aR (F) in subcutaneous adipose tissue. Data are expressed as mean±SEM where **p<0.01 and ***p<0.0001. For correlation, results are presented as Pearson analysis by linear regression.</p

Relationship between subcutaneous C3 mRNA levels, anthropometric and plasma variables.

<p>Correlations are shown between C3 and A) waist circumference (WC), B) Systolic blood pressure (Systolic BP), C) Apolipoprotein B (ApoB), and D) apolipoprotein A1 (ApoA1) in subcutaneous adipose tissue. For correlation, results are presented as Pearson correlation by linear regression.</p

Characteristics of anthropometric and biochemical variables in women.

<p>Range is given as minimum to maximum values.</p><p>Apo: apolipoprotein, BMI: body mass index, BP: blood pressure.</p

Relationship between subcutaneous C3aR mRNA levels, anthropometric and plasma variables.

<p>Correlations are shown between C3aR and A) Waist circumference, B) Systolic blood pressure (Systolic BP), and plasma parameters C) Glucose, D) Apolipoprotein B (ApoB), E) Apolipoprotein A1 (ApoA1), and F) LDL-C/ApoB in subcutaneous adipose tissue. For correlation, results are presented as Pearson analysis by linear regression.</p

Influences of Gestational Obesity on Associations between Genotypes and Gene Expression Levels in Offspring following Maternal Gastrointestinal Bypass Surgery for Obesity

<div><p>Maternal obesity and excess gestational weight gain with compromised metabolic fitness predispose offspring to lifelong obesity and its comorbidities. We demonstrated that compared to offspring born before maternal gastrointestinal bypass surgery (BMS) those born after (AMS) were less obese, with less cardiometabolic risk reflected in the expression and methylation of diabetes, immune and inflammatory pathway genes. Here we examine relationships between gestational obesity and offspring gene variations on expression levels.</p><p>Methods</p><p>Whole-genome genotyping and gene expression analyses in blood of 22 BMS and 23 AMS offspring from 19 mothers were conducted using Illumina HumanOmni-5-Quad and HumanHT-12 v4 Expression BeadChips, respectively. Using PLINK we analyzed interactions between offspring gene variations and maternal surgical status on offspring gene expression levels. Altered biological functions and pathways were identified and visualized using DAVID and Ingenuity Pathway Analysis.</p><p>Results</p><p>Significant interactions (p ≤ 1.22x10^-12) were found for 525 among the 16,060 expressed transcripts: 1.9% of tested SNPs were involved. Gene function and pathway analysis demonstrated enrichment of transcription and of cellular metabolism functions and overrepresentation of cellular stress and signaling, immune response, inflammation, growth, proliferation and development pathways.</p><p>Conclusion</p><p>We suggest that impaired maternal gestational metabolic fitness interacts with offspring gene variations modulating gene expression levels, providing potential mechanisms explaining improved cardiometabolic risk profiles of AMS offspring related to ameliorated maternal lipid and carbohydrate metabolism.</p></div

Expression levels of the target mRNAs in adipose tissue altogether and in normal/overweight and obese groups.

<p>Gene expression was determined by RT-qPCR and is presented as relative expression (R.E.) relative to housekeeping gene GAPDH. A) Expression of genes C3 and C3aR in OM and SC and ratio of SC to OM adipose tissue, B) and C) C3 and C3aR adipose tissue expression in N/Ow group and increasing obesity groups in OM and SC adipose tissue, and D) SC to OM adipose tissue expression level ratio of C3 and C3aR in N/Ow and various grades of obesity groups. Data is expressed as mean±SEM where *p<0.05, **p<0.01 and ***p<0.0001 and pNS indicates not significant.</p

Effects of a DPP4 inhibitor on gene expression of dedifferentiating SC adipocytes.

<p>A) C/EBPα, PPARγ2 and adiponectin gene expression were quantified in mature adipocytes undergoing dedifferentiation (day 5) after a 24-hour treatment with a DPP4 inhibitor (50 μM) or vehicle (Control). N = 13 patients, Matched pair t-test: *p<0.05, § p≤0.10, δ p≤0.15. B) Dose response of DPP4 inhibitor on C/EBPα expression levels in dedifferentiating adipocytes. Cells were treated at days 4 and 6 of ceiling culture in a 6-well plate and harvested at day 6 for qPCR analysis. Repeated measures analysis p-value = 0.06.</p

Most represented transcripts from the list of significant interactions.

<p>Most represented transcripts from the list of significant interactions.</p

Offspring characteristics.

<p>Offspring characteristics.</p