Figure 7.

Schematic representation of hepatocytes with low B12 status upon metformin and adiponectin treatment: (A) Following metformin treatment (dotted line—less activation) with low B12, pAMPKa and pACC levels are decreased with subsequent increase in the levels of SREBF and malonyl-CoA that further inhibits CPT1. In effect, lipogenesis is upregulated whereas fatty acid oxidation (FAO) is decreased, resulting in accumulation of lipids in the hepatocytes. (B) Adiponectin and metformin (solid line—activation) together results in the activation of AMPK. Activated AMPK directly phosphorylates ACC which results in the inhibition of malonyl-CoA. Decreased malonyl-CoA levels facilitate the upregulation of CPT1 and subsequently improves mitochondrion function with increased oxidation of fatty acids (FAO). Similarly, activation of AMPK results in the inactivation of SREBF, which subsequently decreases lipogenesis in hepatocytes (created with BioRender.com).