The Expression/Methylation Profile of Adipogenic and Inflammatory Transcription Factors in Adipose Tissue Are Linked to Obesity-Related Colorectal Cancer.

Obesity is well accepted as crucial risk factor that plays a critical role in the initiation and progression of colorectal cancer (CRC). More specifically, visceral adipose tissue (VAT) in people with obesity could produce chronic inflammation and an altered profile expression of key transcription factors that promote a favorable microenvironment to colorectal carcinogenesis. For this, the aim of this study was to explore the relationship between adipogenic and inflammatory transcription factors in VAT from nonobese, obese, and/or CRC patients. To test this idea, we studied the expression and methylation of CCAAT-enhancer binding protein type alpha (C/EBP-α), peroxisome proliferator-activated receptor gamma (PPAR-γ), peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) in VAT from non-obese control, non-obese CRC subjects, overweight/obese control, and overweight/obese CRC patients and their correlation with anthropometric and biochemical variables. We found decreased expression of C/EBP-α in overweight/obese CRC patients in comparison with overweight/obese control subjects. PGC-1α and NF-κB were overexpressed in CRC patients independently of the BMI. NF-κB promoter was hypomethylated in overweight/obese CRC patients when compared to overweight/obese control individuals. In addition, multiple significant correlations between expression, methylation, and biochemical parameters were found. Finally, linear regression analysis showed that the expression of C/EBP-α and NF-κB and that NF-κB methylation were associated with CRC and able to explain up to 55% of CRC variability. Our results suggest that visceral adipose tissue may be a key factor in tumor development and inflammatory state. We propose C/EBP-α, PGC-1α and NF-κB to be interesting candidates as potential biomarkers in adipose tissue for CRC patients

Association between the APOA2 rs3813627 Single Nucleotide Polymorphism and HDL and APOA1 Levels Through BMI

Background: The interaction between obesity and genetic traits on high density lipoprotein (HDL) levels has been extensively studied. The variance of serum HDL has a strong genetic heritability, although the studied variant only explains a small part of this variation. The goal of this study was to investigate the associations between the apolipoprotein type 2 (APOA2) rs3813627 single nucleotide polymorphism (SNP) and anthropometric and biochemical variables, though body mass index (BMI). Methods: This study included 153 subjects (91 overweight/obese (BMI³25 kg/m2) and 62 non-obese individuals (BMI < 25 kg/m2)). The APOA2 rs3813627 SNP was selected and genotyped. Genotype analysis was performed to analyze the associations between APOA2 SNPs and anthropometric and biochemical variables through BMI. Results: The APOA2 rs3813627 TT genotype was associated with low HDL levels in comparison with the APOA2 rs3813627 GG and GT genotype in overweight/obese individuals, but not in the non-obese subjects (p < 0.05). The same trend was observed in the apolipoprotein type 1 (APOA1) protein levels (p < 0.05). Correlation analysis revealed a negative correlation between HDL and APOA1 levels and APOA2 rs3813627 SNP under recessive model (p < 0.05). The odds ratio for low HDL levels was 3.76 and 3.94 for low APOA1 levels. The mediation analysis of APOA2 rs3813627 SNP through BMI showed a full mediation on HDL and partial mediation on APOA1 levels (p < 0.05). Bioinformatic analysis showed that rs3813627 lies in the APOA2 promoter and overlaps motifs for several bound transcription factors. Conclusion: On the basis of these data, the APOA2 rs3813627 SNP is associated with low HDL and APOA1 levels susceptibility, and this effect was mediated by an increased BMI.This study was supported by the “Centros de Investigación En Red” (CIBER, CB06/03/0018) of the “Instituto de Salud Carlos III” (ISCIII) and grants from ISCIII (PI18/01399; PI15/01350), grants from the Ministry of Economy and Competitiveness (SAF2010-20203) and co-financed by the European Regional Development Fund (FEDER). MMG was the recipient of the Nicolas Monardes Programme from the “Servicio Andaluz de Salud, Junta de Andalucia”, Spain (RC-0001-2018 and C-0029-2023). PHA is supported by a postdoctoral fellowship (Juan de la Cierva-Formación, FJCI-2017-32205). S.M. was the recipient of the Nicolas Monardes Program from the “Servicio Andaluz de Salud, Junta de Andalucía”, Spain (C-0050-2017).Ye