(P31-032-23) Methylation Levels of Genes in the INSR-A Branch of Insulin Signaling Pathway Altered by Saturated and Polyunsaturated Fatty Acids in Adipogenesis

Objectives: Obesity is a chronic condition caused by accumulation of extra energy in the body as lipids and is a risk factor of type 2 diabetes and several other chronic conditions. Insulin signaling pathway may be affected by epigenetic modifications including DNA methylation induced by higher lipid profile in development of obesity.

Methods: Genomic DNA samples were extracted from differentiating 3T3-L1 pre-adipocytes treated with each of the two saturated fatty acids and a polyunsaturated fatty acid to mimic conditions in development of obesity. DNA methylation sequencing was used to analyze methylation levels of genes in the INSR-A branch (regulating proliferation and differentiation) and the INSR-B branch (regulating metabolism) of the insulin signaling pathway during adipogenesis. 

Results: Saturated fatty acids reduce methylation levels of the genes including IRS-1, MEK1, MEK2, and ERK2 in the INSR-A branch significantly and also slightly reduce methylation levels of the genes downstream of IRS-1 in the INSR-B branch including PIK3CA, PDE3B, and SLC2A4 in adipogenesis. The saturated and polyunsaturated fatty acids cause reduced methylation levels of genes in the INSR-A branch in a similar pattern.

Conclusions: These results indicate that saturated fatty acids may enhance adipogenesis via reducing methylation levels of the genes in the INSR-A branch of insulin signaling pathway in adipogenesis.

Funding Sources: This work was supported by startup funds from Saint Louis University to YL and by the Washington University Institute of Clinical and Translational Sciences which is, in part, supported by the NIH/National Center for Advancing Translational Sciences (NCATS), CTSA grant #UL1TR002345.