Figure 3.

Relationship of liver steatosis with the VLDL secretory pathway. One important feature of hepatocytes is the ability to efficiently export excess triglycerides and other lipids as VLDL. (A) If the rate of VLDL assembly and secretion is limiting, triglycerides are diverted to lipid droplets and the extent of steatosis increases. Impairment of VLDL secretion can be caused by naturally occurring mutations in proteins pivotal for VLDL production (APOB, MTTP, TM6SF2), by insulin action, lack of the major VLDL surface lipid phosphatidylcholine and possibly by reduced polyunsaturated fatty acids (PUFA) or by endoplasmic reticulum stress. (B) Clinical studies report that VLDL secretion, and in parallel dyslipidemia, increase with progression of MAFLD along with liver steatosis. A plateau is reached at the MAFL or the steatohepatitis stage, probably because the VLDL secretory capacity has reached a limit. In advanced liver disease such as cirrhosis VLDL secretion is reduced again, likely reflecting the loss of functional hepatocytes.