We hypothesized that decreased SLC2A4 gene expression in the VAT of obese humans with impaired glycemic control (high HbA1c) emerges from a fatty-acid-induced (dietary or obesity-associated) increase in DNA methylation in a SLC2A4 enhancer region spanning several SP1 and SREBPF-1 binding motifs. The gene discussed is SP1; the disease is obesity due to melanocortin 4 receptor deficiency.