Changes in DNA Methylation and Gene Expression of Insulin and Obesity-Related Gene PIK3R1 after Roux-en-Y Gastric Bypass

Int J Mol Sci. 2020 Jun 24;21(12):4476. doi: 10.3390/ijms21124476.

Abstract

Weight regulation and the magnitude of weight loss after a Roux-en-Y gastric bypass (RYGB) can be genetically determined. DNA methylation patterns and the expression of some genes can be altered after weight loss interventions, including RYGB. The present study aimed to evaluate how the gene expression and DNA methylation of PIK3R1, an obesity and insulin-related gene, change after RYGB. Blood samples were obtained from 13 women (35.9 ± 9.2 years) with severe obesity before and six months after surgical procedure. Whole blood transcriptome and epigenomic patterns were assessed by microarray-based, genome-wide technologies. A total of 1966 differentially expressed genes were identified in the pre- and postoperative periods of RYGB. From these, we observed that genes involved in obesity and insulin pathways were upregulated after surgery. Then, the PIK3R1 gene was selected for further RT-qPCR analysis and cytosine-guanine nucleotide (CpG) sites methylation evaluation. We observed that the PI3KR1 gene was upregulated, and six DNA methylation CpG sites were differently methylated after bariatric surgery. In conclusion, we found that RYGB upregulates genes involved in obesity and insulin pathways.

Keywords: DNA methylation; bariatric surgery; gene expression; insulin; microarray; obesity; weight loss.

MeSH terms

  • Adult
  • Class Ia Phosphatidylinositol 3-Kinase / genetics*
  • Class Ia Phosphatidylinositol 3-Kinase / metabolism
  • DNA Methylation*
  • Female
  • Gastric Bypass / methods*
  • Gene Expression Regulation*
  • Humans
  • Insulin / genetics*
  • Insulin / metabolism
  • Obesity, Morbid / genetics*
  • Obesity, Morbid / pathology
  • Obesity, Morbid / surgery
  • Transcriptome

Substances

  • Insulin
  • PIK3R1 protein, human
  • Class Ia Phosphatidylinositol 3-Kinase