Acetyl-CoA is the building block of lipid synthesis. The pyruvate made in glycolysis is essential for production of acetyl-CoA by the pyruvate dehydrogeanse complex. Acetyl-CoA is then used by another enzyme, acetyl-CoA carboxylase (ACC), to initiate fatty acid biosynthesis. ACC converts acetyl-CoA to malonyl-CoA so that chains of sixteen carbons can be elongated. Fatty acid chains are then formed via the fatty acid synthase complex (Figure 3). The fatty acids can either be incorporated into lipid membranes or packaged with specific lipoproteins for distribution, depending on the cell's needs (Nelson and Cox , 2004). When an individual's diet is rich in fatty acids and it exceeds the necessary amount, the triacylglycerols are packaged with lipid proteins to form VLDL for transportation to non-liver tissues.

Figure 3: The formation of long chain fatty acids starting with acetyl-CoA. [Nelson and Cox , page 793, 2004]

Very low density lipoproteins contribute to bad cholesterol. The VLDL that is formed in the liver is detrimental to the body when it is stripped of its triacylglycerols by extra-hepatic tissues (Figure 4). The remnants, which are cholesterol rich, are low-density lipoproteins, LDL. LDL is the main source of bad cholesterol. Protecting against the ill effects of high cholesterol levels therefore requires targeting VLDL formation, a precursor to LDL (Nelson and Cox, 2004).

Figure 4: Lipoprotein Degradation in extra-hepatic tissues after being excreted by the liver. [Nelson and Cox , page 822, 2004]

Astrocytes are non-neuronal cells in the brain. They are star-shaped cells, particularly in the hypothalamus, that surround neurons. The main function of astrocytes is to provide the neurons with energy by oxidizing glucose (Figure 5). Glucose is degraded to pyruvate in astrocytes where it is then transported to the liver to form acetyl-CoA. When brain glucose metabolism is stimulated, the lactate dehydrogenase complex converts lactate to pyruvate and activates the ATP-sensitive potassium channels. Activating the ATP-sensitive potassium channels in the liver affects the SCD1 activity and decreases the secretion of VLDL (Lam, et al., 2007).

Figure 5: The metabolic pathway that connects glucose metabolism in the brain to lipid secretion in the liver. [Figure 1a, Lam, et al., 2007]