Reduced Intra- and Extracellular Circulating Postprandial Lysosomal Acid Lipase Activity in Patients with MASLD

Area of Science:

• Biochemistry
• Hepatology
• Metabolic Disorders

Background:

• Low fasting blood lysosomal acid lipase (LAL) activity is linked to metabolic hepatic steatosis.
• Metabolic-dysfunction-associated steatotic liver disease (MASLD) is a growing concern in metabolic health.

Purpose of the Study:

• To measure LAL activity in blood and plasma before and after an oral fat tolerance test (OFTT) in patients with MASLD.
• To investigate the relationship between LAL activity, MASLD, and the patatin-like phospholipase 3 (PNPLA3) variant.

Main Methods:

• Assessed LAL activity in blood and plasma using a fluorimetric method.
• Conducted an OFTT in 17 MASLD patients and 26 controls.
• Genotyped participants for the PNPLA3 rs738409 variant via RT-PCR.

Main Results:

• MASLD patients showed significantly lower fasting and postprandial blood LAL activity compared to controls, especially those with the PNPLA3 variant.
• Plasma extracellular LAL activity was also reduced in MASLD patients both in fasting and postprandial states.
• The negative correlation between LAL activity and postprandial triglycerides was absent in MASLD patients but present in controls.

Conclusions:

• MASLD patients exhibit diminished LAL activity in both blood and plasma, irrespective of meal intake.
• The study highlights a loss of the normal inverse relationship between circulating LAL levels and postprandial hypertriglyceridemia in MASLD.
• The PNPLA3 variant appears to influence the observed LAL activity differences in MASLD.