Figure 2.

The decreased expression and activity of Sirtuin1 is a common molecular hallmark in a high fat diet and methyl donor deficiency (MDD). Sirtuin1 targets the acetylation of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) and has a complementary role with GCN5 acetylase, AMP kinase and protein arginine methyltransferase (PRMT1) in the regulation of PGC1α activation of nuclear receptors, including PPARα, ERRα, HNF-4α and VDR. PGC1α is phosphorylated and acetylated under the control of AMP kinase (AMPK), GCN5 acetylase and SIRT1 deacetylase. High fat diet and over nutrition decrease activity of AMP kinase, through high intracellular ATP levels, leading to decreased phosphorylation of PGC-1 α. It produces hyperacetylation of PGC-1α through increased expression of GCN5 and decreased expression and activity of SIRT1. MDD produces similar effects through decreased SIRT1 and PRMT1.