Biomarkers and subtypes of deranged lipid metabolism in non-alcoholic fatty liver disease

Figure 1 Lipid metabolism. The mobilization of fatty acids (FA) from their triglyceride (TG) storage in the adipose tissue is promoted by TG lipases. The resultant FA are then released into the blood and taken up by hepatocytes. Other sources of hepatic FA are the dietary lipids in chylomicrons and de novo lipogenesis induced by carbohydrates. These FA are metabolized by mitochondrial or peroxisomal β-oxidation, accumulated in the cytoplasm inducing lipotoxicity, or subsequently elongated, desaturated and re-esterified for synthesis of complex lipids such us phospholipids (PL), diglycerides or TG. Some of the re-esterified TG are packed into very low-density lipoproteins combined with apolipoprotein-B and exported into circulation. This process is regulated by microsomal triglyceride transfer protein and accompanied by encapsulating the neutral lipid core with a PL monolayer enriched in phosphatidylcholine molecules containing polyunsaturated FA. Enzyme reactions regulated by S-adenosylmethionine (SAMe) and pathways in which SAMe deficiency may lead to the accumulation of TG and progression to nonalcoholic steatohepatitis are indicated in blue. APOB: Apolipoprotein-B; DG: Diglycerides; ER: Endoplasmic reticulum; FA: Fatty acids; MTTP: Microsomal triglycerides transfer protein; PC-PUFA: Phosphatidylcholines containing polyunsaturated fatty acids; PL: Phospholipids; SAMe: S-adenosylmethionine; TG: Triglycerides; VLDL: Very low-density lipoproteins.