fig3

Figure 3. Diagram of cholesterol and FA metabolic pathways. Cholesterol is either imported as LDL through LDLR or it is synthesized through the mevalonate pathway. From there, cholesterol serves as a precursor to vitamin D, steroid hormones, and bile acids or it integrates into the cellular membrane to regulate membrane fluidity and cell signaling. Excess intracellular cholesterol is exported through ABCA or esterified to form CE, which are stored in lipid droplets. FAs are imported via CD36 and fatty acid transport proteins or synthesized through citrate from the TCA cycle. Palmitate, the initial FA that is formed, undergoes elongation and desaturation by ELOVL and FADS enzymes, respectively, to form a variety of FAs with varying chain lengths and degrees of unsaturation. FAs participate in energy metabolism through the FA b-oxidation pathway that generates acetyl-CoA to drive the TCA cycle. Similar to cholesterol, fatty acids are important components of cellular membranes via the formation of phospholipids and excess fatty acids are converted to TG and stored in lipid droplets. ABCA: ATP-binding cassette transporters; ACAT1: Acyl-CoA cholesterol acyl transferase 1; ACC: acetyl-CoA carboxylase; ACLY: ATP citrate lyase; ATP: adenosine triphosphate; CE: cholesteryl esters; ELOVL: elongation of very long chain fatty acids protein; FA: fatty acid; FADS: fatty acid desaturase; FATP: fatty acid transport protein; FASN: fatty acid synthase; FPP: farnesyl diphosphate; LDL: low-density lipoprotein; LDLR: low-density lipoprotein receptor; MUFA: mono-unsaturated fatty acid; PUFA: poly-unsaturated fatty acid; SQS: squalene synthase; SQLE: squalene epoxidase; TCA: tricarboxylic acid; TG: triglyceride.