Figure 7

A proposed mechanism by which metformin reduces the accumulation of lipids in endothelial cells. Low levels of fatty acids [low fat diet (LFD)] are metabolized by mitochondria or transported to peripheral tissues (left). When an excess amount of fatty acids are provided [high fat diet (HFD)], mitochondrial dysfunction, and impaired autophagy (lipophagy) reduces fatty acid oxidation and increases the intracellular pool of fatty acids/acyl-CoA, which leads to accumulation of lipid droplets. This stressful condition stimulates pro-inflammatory responses (middle). Treatment with metformin stimulates fatty acid oxidation and autophagy (lipophagy) which reduces the accumulation of lipid droplets and the intracellular pool of fatty acids. This action of metformin contributes to the reduction of pro-inflammatory response (right).