CES1

CES1 (carboxylesterase 1) is a major serine hydrolase highly expressed in the liver and functions in the hydrolysis of ester-, amide-, and lipid-containing substrates, thereby contributing to both xenobiotic metabolism and endogenous lipid turnover^[1][1]. Mechanistically, CES1 hydrolyzes triacylglycerols and cholesteryl esters and participates in pathways controlling hepatic lipid homeostasis, fatty acid utilization, and lipid droplet dynamics^[2][3]. Therefore, CES1 has become an important target for studies investigating the interface between drug metabolism and metabolic regulation^[1][2]. In disease-related models, genetic deletion or functional disruption of Ces1/CES1 alters lipid metabolism, promotes adipose lipid accumulation, impairs glucose tolerance, and contributes to hepatic metabolic abnormalities, supporting its relevance to metabolic syndrome research^[2][3]. In hepatocellular carcinoma models, inhibition or genetic ablation of CES1 reprograms lipid signaling, reduces polyunsaturated fatty acid-associated pathways, and alters mitochondrial function, linking CES1 activity to tumor progression and therapeutic response^[4]. Compared with the related isoform CES2, CES1 is the predominant hepatic carboxylesterase and displays distinct substrate preferences and tissue distribution patterns, making isoform selectivity an important consideration in mechanistic studies and drug development^[1][1]. For experimental applications, selective CES1 inhibitors such as WWL229 have been used to investigate CES1-dependent lipid metabolism and disease-associated signaling pathways^[4].