Hepatic triglyceride synthesis enzymes (HTGSE)

Hepatic triglyceride synthesis enzymes refer to a group of enzymes involved in the Kennedy pathway, which is the primary route for the synthesis of triacylglycerols in the liver. Key enzymes in this group include Glycerol-3-phosphate acyltransferase (GPAT), 1-acyl-sn-glycerol-3-phosphate acyltransferase (AGPAT), Phosphatidic acid phosphatase (PAP/Lipin), and Diacylglycerol O-acyltransferase (DGAT1 and DGAT2) (Source: PMID: 22434599, 21731050). These enzymes catalyze the sequential acylation of a glycerol-3-phosphate backbone, with DGAT2 serving as the final and rate-limiting step for hepatic triglyceride formation (Source: NIH/NCBI). Dysregulation of these enzymes leads to excessive accumulation of lipid droplets in hepatocytes, a hallmark of Metabolic dysfunction-associated steatotic liver disease (MASLD/MASH). Consequently, these enzymes have become significant therapeutic targets; for instance, DGAT2 inhibitors like Ervogastat are being clinical evaluated to reduce liver fat content and prevent progression to fibrosis (Source: Pfizer, ClinicalTrials.gov). While targeting the final steps of synthesis can effectively lower hepatic steatosis, pharmacological intervention must balance efficacy with potential side effects such as gastrointestinal intolerance, particularly observed with non-selective acyltransferase inhibition (Source: PubMed Central).

Other names

Kennedy pathway enzymesTriglyceride synthesis pathwayGlycerolipid synthesis enzymesDiacylglycerol O-acyltransferaseGlycerol-3-phosphate acyltransferase1-acyl-sn-glycerol-3-phosphate acyltransferasePhosphatidic acid phosphatase

Inhibition of specific enzymes within the Kennedy pathway, primarily DGAT2 or DGAT1, to reduce the final esterification step of triglyceride synthesis, thereby decreasing hepatic fat accumulation and VLDL production.